{ "schema_version": "2.0.0", "benchmark_id": "cftr-variant-predictor-and-structural-domain-atlas-v2", "tier": "Tier T2 Verified Fixture, UniProt P13569 & Cryo-EM Structural Coordinate Atlas", "grounding_note": "Evaluates 17 recorded ClinVar variation records (across 9 distinct CFTR protein changes), MyVariant.info annotations, and all 209 annotated natural variants in UniProt P13569 across RefSeq NM_000492.4 (27 exons) and 4 superposed human CFTR Cryo-EM structures (PDB 6MSM, 5UAK, 8EIQ, 8EJ1). No synthetic scores or unverified LoRA weights are used; every missing annotation is explicitly recorded as 'not stated'.", "summary_metrics": { "total_clinvar_records_evaluated": 17, "distinct_clinvar_protein_changes": 9, "total_uniprot_natural_variants_mapped": 209, "uniprot_placed_in_6msm_cryoem": 191, "uniprot_unplaced_disordered_region": 18, "uniprot_near_splice_junction_le_3aa": 17, "domains_represented": 5, "total_cftr_domains_defined": 6, "consequence_class_counts": { "inframe_deletion": 2, "missense_snv": 6, "nonsense_premature_termination": 5, "frameshift_indel": 1, "complex_haplotype": 3 }, "multi_nucleotide_protein_groups_count": 4 }, "key_benchmark_findings": [ { "finding_id": "VF-1", "label": "[observed]", "summary": "Sequence conservation vs. structural benignity split on Lasso-motif VUS R31L (VCV000054087, Exon 2/27): CADD Phred is 22.9 (top <1% conserved, GERP++ RS=437.4), whereas PolyPhen-2 (0.131, benign) and SIFT (0.13, tolerated) classify p.Arg31Leu as benign, matching ClinVar expert panel 'Uncertain significance'." }, { "finding_id": "VF-2", "label": "[observed]", "summary": "Codon degeneracy & review-tier asymmetry across identical protein changes: N1303K (NBD2, Exon 24/27), Y1092* (TMD2, Exon 20/27), W1282* (NBD2, Exon 23/27), and F508del (NBD1, Exon 11/27) each map to multiple ClinVar Variation IDs with distinct cDNA changes and review statuses (e.g., N1303K c.3909C>G [uid 7136, practice guideline, 52 SCVs] vs. c.3909C>A [uid 4818550, single submitter, 1 SCV])." }, { "finding_id": "VF-3", "label": "[observed]", "summary": "ClinVar 'drug response' classification on TMD2 pore/hinge missense variant D1152H (VCV000035867, Exon 21/27, review_status: reviewed by expert panel, trait: 'ivacaftor response - Efficacy'): binary pathogenic/benign classifiers misrepresent pharmacogenomic residual-function variants without a separate modulator-response label." }, { "finding_id": "VF-4", "label": "[computed]", "summary": "Across the 209 UniProt P13569 natural variants superposed onto Cryo-EM structures 6MSM/5UAK/8EIQ/8EJ1, 191 are resolved in 3D C-alpha coordinates in 6MSM while 18 fall in unplaced intrinsically disordered regions (primarily the R-domain, residues 631-845, Exon 14/27), and 17 lie within <=3 codons of an exon-intron boundary." } ], "multi_nucleotide_degeneracy_audit": { "F508del": [ { "clinvar_variation_id": "7105", "cdna_change": "c.1521_1523del", "classification": "Pathogenic", "review_status": "practice guideline", "supporting_scv_count": 101 }, { "clinvar_variation_id": "4072070", "cdna_change": "c.1522_1524del", "classification": "Pathogenic", "review_status": "criteria provided, single submitter", "supporting_scv_count": 1 } ], "W1282*": [ { "clinvar_variation_id": "7129", "cdna_change": "c.3846G>A", "classification": "Pathogenic", "review_status": "practice guideline", "supporting_scv_count": 43 }, { "clinvar_variation_id": "983867", "cdna_change": "c.3845G>A", "classification": "Likely pathogenic", "review_status": "criteria provided, single submitter", "supporting_scv_count": 1 } ], "N1303K": [ { "clinvar_variation_id": "7136", "cdna_change": "c.3909C>G", "classification": "Pathogenic", "review_status": "practice guideline", "supporting_scv_count": 52 }, { "clinvar_variation_id": "4818550", "cdna_change": "c.3909C>A", "classification": "Likely pathogenic", "review_status": "criteria provided, single submitter", "supporting_scv_count": 1 } ], "Y1092*": [ { "clinvar_variation_id": "7211", "cdna_change": "c.3276C>G", "classification": "Pathogenic", "review_status": "reviewed by expert panel", "supporting_scv_count": 6 }, { "clinvar_variation_id": "38728", "cdna_change": "c.3276C>A", "classification": "Pathogenic", "review_status": "reviewed by expert panel", "supporting_scv_count": 26 }, { "clinvar_variation_id": "375475", "cdna_change": "c.3276C>R", "classification": "Pathogenic", "review_status": "no assertion criteria provided", "supporting_scv_count": 1 } ] }, "structural_domain_breakdown": [ { "domain_id": "Lasso_N_terminal", "name": "Lasso Motif / N-terminal interfacial region", "residue_range": "1-80", "uniprot_ref": "UniProtKB:P13569:1-80", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "clinvar_fixture_records_count": 2, "uniprot_natural_variants_count": 11, "classifications": { "Conflicting classifications of pathogenicity": 1, "Uncertain significance": 1 }, "consequence_classes": { "missense_snv": 2 }, "variants": [ "R31C (c.91C>T, VCV:35893)", "R31L (c.92G>T, VCV:54087)" ] }, { "domain_id": "TMD1", "name": "Transmembrane Domain 1 (TM1-TM6 & ICL1/ICL2)", "residue_range": "81-380", "uniprot_ref": "UniProtKB:P13569:81-380", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "clinvar_fixture_records_count": 3, "uniprot_natural_variants_count": 54, "classifications": { "Pathogenic": 3 }, "consequence_classes": { "missense_snv": 1, "frameshift_indel": 1, "complex_haplotype": 1 }, "variants": [ "R117H (c.350G>A, VCV:7109)", "R104fs (c.310del, VCV:53653)", "R117H (c.350G>A, VCV:209047)" ] }, { "domain_id": "NBD1", "name": "Nucleotide-Binding Domain 1", "residue_range": "381-630", "uniprot_ref": "UniProtKB:P13569:381-630", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "clinvar_fixture_records_count": 2, "uniprot_natural_variants_count": 55, "classifications": { "Pathogenic": 2 }, "consequence_classes": { "inframe_deletion": 2 }, "variants": [ "F508del (c.1521_1523del, VCV:7105)", "F508del (c.1522_1524del, VCV:4072070)" ] }, { "domain_id": "R_domain", "name": "Regulatory (R) Domain (intrinsically disordered)", "residue_range": "631-845", "uniprot_ref": "UniProtKB:P13569:631-845", "pdb_refs": [ "5UAK", "6MSM" ], "clinvar_fixture_records_count": 0, "uniprot_natural_variants_count": 15, "classifications": {}, "consequence_classes": {}, "variants": [] }, { "domain_id": "TMD2", "name": "Transmembrane Domain 2 (TM7-TM12 & ICL3/ICL4)", "residue_range": "846-1190", "uniprot_ref": "UniProtKB:P13569:846-1190", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "clinvar_fixture_records_count": 4, "uniprot_natural_variants_count": 50, "classifications": { "Pathogenic": 3, "drug response": 1 }, "consequence_classes": { "nonsense_premature_termination": 3, "missense_snv": 1 }, "variants": [ "Y1092* (c.3276C>G, VCV:7211)", "D1152H (c.3454G>C, VCV:35867)", "Y1092* (c.3276C>A, VCV:38728)", "Y1092* (c.3276C>R, VCV:375475)" ] }, { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "residue_range": "1191-1480", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "clinvar_fixture_records_count": 5, "uniprot_natural_variants_count": 24, "classifications": { "Pathogenic": 3, "Likely pathogenic": 2 }, "consequence_classes": { "nonsense_premature_termination": 2, "missense_snv": 2, "complex_haplotype": 1 }, "variants": [ "W1282* (c.3846G>A, VCV:7129)", "N1303K (c.3909C>G, VCV:7136)", "W1282* (c.3845G>A, VCV:983867)", "W1282*, R1283M (c.3846G>A, VCV:1300168)", "N1303K (c.3909C>A, VCV:4818550)" ] } ], "variant_records": [ { "clinvar_variation_id": { "value": "7105", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000007105.213", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.3(CFTR):c.1521_1523del (p.Phe508del)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "Deletion", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.1521_1523del", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "F508del", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title (protein_change empty on ClinVar 7105/634837)]" }, "residue_position": { "value": 508, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 11, "exon_label": "11/27", "exon_codon_span": "465-528", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD1", "name": "Nucleotide-Binding Domain 1", "uniprot_ref": "UniProtKB:P13569:381-630", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "ATP binding and canonical F508 cotranslational folding hub; contacts ICL1 and ICL4." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK" ], "delta_ca_6msm_vs_5uak_angstrom": 9.19, "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": 0.0, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "inframe_deletion", "canonical_cftr_class_note": "Class II (in-frame deletion affecting domain folding/maturation, e.g. F508del in NBD1).", "source": "[computed from esummary:protein_change / HGVS p.*del]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "practice guideline", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2004/03/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 101, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "7109", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000007109.185", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.350G>A (p.Arg117His)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.350G>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "R117H", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 117, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 4, "exon_label": "4/27", "exon_codon_span": "92-163", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD1", "name": "Transmembrane Domain 1 (TM1-TM6 & ICL1/ICL2)", "uniprot_ref": "UniProtKB:P13569:81-380", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM1, TM6) and intracellular coupling helices (ICL1 contacts NBD1; ICL2 contacts NBD2)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "practice guideline", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2004/03/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 49, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "7129", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000007129.173", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3846G>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "W1282*", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1282, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 23, "exon_label": "23/27", "exon_codon_span": "1210-1292", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Catalytic ATP hydrolysis site via NBD1:NBD2 head-to-tail dimerization; late cotranslational folding domain (N1303)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 43.8, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "nonsense_premature_termination", "canonical_cftr_class_note": "Class I (premature termination codon / nonsense-mediated decay candidate).", "source": "[computed from esummary:protein_change / HGVS p.*]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "practice guideline", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2004/03/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 43, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "7136", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000007136.180", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3909C>G (p.Asn1303Lys)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3909C>G", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "N1303K", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1303, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 24, "exon_label": "24/27", "exon_codon_span": "1293-1326", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Catalytic ATP hydrolysis site via NBD1:NBD2 head-to-tail dimerization; late cotranslational folding domain (N1303)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.7, "dist_to_f508_in_6msm_angstrom": 35.56, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "practice guideline", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2004/03/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 52, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "7211", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000007211.12", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3276C>G (p.Tyr1092Ter)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3276C>G", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "Y1092*", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1092, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 20, "exon_label": "20/27", "exon_codon_span": "1041-1123", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD2", "name": "Transmembrane Domain 2 (TM7-TM12 & ICL3/ICL4)", "uniprot_ref": "UniProtKB:P13569:846-1190", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM8, TM12), ivacaftor potentiator cleft (TM8 hinge), and ICL4 socket for NBD1 F508." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.96, "delta_ca_6msm_vs_8eiq_angstrom": 0.44, "dist_to_f508_in_6msm_angstrom": 35.17, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "nonsense_premature_termination", "canonical_cftr_class_note": "Class I (premature termination codon / nonsense-mediated decay candidate).", "source": "[computed from esummary:protein_change / HGVS p.*]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2017/03/17 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 6, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "35867", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000035867.107", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3454G>C (p.Asp1152His)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3454G>C", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "D1152H", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1152, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 21, "exon_label": "21/27", "exon_codon_span": "1124-1175", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD2", "name": "Transmembrane Domain 2 (TM7-TM12 & ICL3/ICL4)", "uniprot_ref": "UniProtKB:P13569:846-1190", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM8, TM12), ivacaftor potentiator cleft (TM8 hinge), and ICL4 socket for NBD1 F508." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.06, "delta_ca_6msm_vs_8eiq_angstrom": 0.46, "dist_to_f508_in_6msm_angstrom": 43.57, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "drug response", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2021/03/24 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 46, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "35893", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:uid]" }, "accession_version": { "value": "VCV000035893.57", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.91C>T (p.Arg31Cys)", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:obj_type]" }, "cdna_change": { "value": "c.91C>T", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "R31C", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:protein_change]" }, "residue_position": { "value": 31, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 2, "exon_label": "2/27", "exon_codon_span": "19-55", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "Lasso_N_terminal", "name": "Lasso Motif / N-terminal interfacial region", "uniprot_ref": "UniProtKB:P13569:1-80", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Wraps around TMD1/TMD2 transmembrane helices and contacts R-domain; ETI corrector binding vicinity in TMD1." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 37.34, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "Conflicting classifications of pathogenicity", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.description]" }, "review_status": { "value": "criteria provided, conflicting classifications", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2026/05/01 00:00", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 21, "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "38728", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000038728.59", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3276C>A (p.Tyr1092Ter)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3276C>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "Y1092*", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1092, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 20, "exon_label": "20/27", "exon_codon_span": "1041-1123", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD2", "name": "Transmembrane Domain 2 (TM7-TM12 & ICL3/ICL4)", "uniprot_ref": "UniProtKB:P13569:846-1190", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM8, TM12), ivacaftor potentiator cleft (TM8 hinge), and ICL4 socket for NBD1 F508." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.96, "delta_ca_6msm_vs_8eiq_angstrom": 0.44, "dist_to_f508_in_6msm_angstrom": 35.17, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "nonsense_premature_termination", "canonical_cftr_class_note": "Class I (premature termination codon / nonsense-mediated decay candidate).", "source": "[computed from esummary:protein_change / HGVS p.*]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2017/03/17 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 26, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "53653", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:uid]" }, "accession_version": { "value": "VCV000053653.7", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.310del (p.Arg104fs)", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:title]" }, "obj_type": { "value": "Deletion", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:obj_type]" }, "cdna_change": { "value": "c.310del", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "R104fs", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:protein_change]" }, "residue_position": { "value": 104, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 4, "exon_label": "4/27", "exon_codon_span": "92-163", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD1", "name": "Transmembrane Domain 1 (TM1-TM6 & ICL1/ICL2)", "uniprot_ref": "UniProtKB:P13569:81-380", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM1, TM6) and intracellular coupling helices (ICL1 contacts NBD1; ICL2 contacts NBD2)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.51, "delta_ca_6msm_vs_8eiq_angstrom": 0.33, "dist_to_f508_in_6msm_angstrom": 74.64, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "frameshift_indel", "canonical_cftr_class_note": "Class I (frameshift insertion/deletion leading to premature termination).", "source": "[computed from esummary:protein_change / HGVS p.*fs]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2017/03/17 00:00", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 6, "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "54087", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:uid]" }, "accession_version": { "value": "VCV000054087.29", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.92G>T (p.Arg31Leu)", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:obj_type]" }, "cdna_change": { "value": "c.92G>T", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "R31L", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:protein_change]" }, "residue_position": { "value": 31, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 2, "exon_label": "2/27", "exon_codon_span": "19-55", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "Lasso_N_terminal", "name": "Lasso Motif / N-terminal interfacial region", "uniprot_ref": "UniProtKB:P13569:1-80", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Wraps around TMD1/TMD2 transmembrane helices and contacts R-domain; ETI corrector binding vicinity in TMD1." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 37.34, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "Uncertain significance", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2017/03/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 13, "source": "[tools/variant_profile/fixtures/esummary_54087_53653_35893.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "[tools/variant_profile/fixtures/myvariant_CFTR_R31L.json]", "cadd_phred": { "value": 22.9, "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": 3.36173, "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": 102, "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "2/27", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "ndomain", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "benign", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": 0.131, "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "tolerated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": 0.13, "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "evaluated_from_fixture", "cadd_ge_20_deleterious": true, "polyphen_damaging": false, "sift_deleterious": false, "predictors_disagree_internally": true, "clinvar_reference": "Uncertain significance", "predictor_agreement_note": "ClinVar classification is 'Uncertain significance'. CADD Phred=22.9 (deleterious>=20: True), PolyPhen-2='benign' (damaging: False), SIFT='tolerated' (deleterious: False). Sequence conservation (CADD>=20) diverges from structural/PSSM benign calls (PolyPhen-2/SIFT) on this VUS." } }, { "clinvar_variation_id": { "value": "209047", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000209047.3", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.3(CFTR):c.[350G>A;1210-12[5]]", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "Haplotype", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.350G>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "R117H", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 117, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 4, "exon_label": "4/27", "exon_codon_span": "92-163", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD1", "name": "Transmembrane Domain 1 (TM1-TM6 & ICL1/ICL2)", "uniprot_ref": "UniProtKB:P13569:81-380", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM1, TM6) and intracellular coupling helices (ICL1 contacts NBD1; ICL2 contacts NBD2)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "complex_haplotype", "canonical_cftr_class_note": "Complex allele / cis-haplotype (e.g. R117H;5T or F508del;I1027T); phenotype depends on cis-modifier.", "source": "[computed from esummary:obj_type and esummary:title]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "not stated", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "375475", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000375475.1", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3276C>R (p.Tyr1092Ter)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3276C>R", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "Y1092*", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1092, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 20, "exon_label": "20/27", "exon_codon_span": "1041-1123", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "TMD2", "name": "Transmembrane Domain 2 (TM7-TM12 & ICL3/ICL4)", "uniprot_ref": "UniProtKB:P13569:846-1190", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Forms anion pore lining (TM8, TM12), ivacaftor potentiator cleft (TM8 hinge), and ICL4 socket for NBD1 F508." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.96, "delta_ca_6msm_vs_8eiq_angstrom": 0.44, "dist_to_f508_in_6msm_angstrom": 35.17, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "nonsense_premature_termination", "canonical_cftr_class_note": "Class I (premature termination codon / nonsense-mediated decay candidate).", "source": "[computed from esummary:protein_change / HGVS p.*]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "no assertion criteria provided", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "1993/01/01 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "634837", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000634837.2", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.3(CFTR):c.[1521_1523delCTT;3080T>C]", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "Haplotype", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.1521_1523del", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "not stated", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": "not stated", "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": "not stated", "exon_label": "not stated", "exon_codon_span": "not stated", "near_splice_junction_le_3aa": "not stated", "source": "[not stated]" }, "structural_domain": { "domain_id": "not stated", "name": "not stated", "uniprot_ref": "not stated", "pdb_refs": [], "structural_role": "not stated" }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "source": "not stated" }, "molecular_mechanism": { "consequence_class": "complex_haplotype", "canonical_cftr_class_note": "Complex allele / cis-haplotype (e.g. R117H;5T or F508del;I1027T); phenotype depends on cis-modifier.", "source": "[computed from esummary:obj_type and esummary:title]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2019/03/11 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "983867", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV000983867.3", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3845G>A (p.Trp1282Ter)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3845G>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "W1282*", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1282, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 23, "exon_label": "23/27", "exon_codon_span": "1210-1292", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Catalytic ATP hydrolysis site via NBD1:NBD2 head-to-tail dimerization; late cotranslational folding domain (N1303)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 43.8, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "nonsense_premature_termination", "canonical_cftr_class_note": "Class I (premature termination codon / nonsense-mediated decay candidate).", "source": "[computed from esummary:protein_change / HGVS p.*]" }, "clinvar_classification": { "description": { "value": "Likely pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "criteria provided, single submitter", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2019/09/29 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "1300168", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV001300168.2", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.[3846G>A;3848G>T]", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "Haplotype", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3846G>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "W1282*, R1283M", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1282, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 23, "exon_label": "23/27", "exon_codon_span": "1210-1292", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Catalytic ATP hydrolysis site via NBD1:NBD2 head-to-tail dimerization; late cotranslational folding domain (N1303)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 43.8, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "complex_haplotype", "canonical_cftr_class_note": "Complex allele / cis-haplotype (e.g. R117H;5T or F508del;I1027T); phenotype depends on cis-modifier.", "source": "[computed from esummary:obj_type and esummary:title]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "reviewed by expert panel", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2020/01/10 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "4072070", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV004072070.1", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.1522_1524del (p.Phe508del)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "Deletion", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.1522_1524del", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "F508del", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 508, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 11, "exon_label": "11/27", "exon_codon_span": "465-528", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD1", "name": "Nucleotide-Binding Domain 1", "uniprot_ref": "UniProtKB:P13569:381-630", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "ATP binding and canonical F508 cotranslational folding hub; contacts ICL1 and ICL4." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK" ], "delta_ca_6msm_vs_5uak_angstrom": 9.19, "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": 0.0, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "inframe_deletion", "canonical_cftr_class_note": "Class II (in-frame deletion affecting domain folding/maturation, e.g. F508del in NBD1).", "source": "[computed from esummary:protein_change / HGVS p.*del]" }, "clinvar_classification": { "description": { "value": "Pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "criteria provided, single submitter", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2025/06/28 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } }, { "clinvar_variation_id": { "value": "4818550", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:uid]" }, "accession_version": { "value": "VCV004818550.1", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:accession_version]" }, "title": { "value": "NM_000492.4(CFTR):c.3909C>A (p.Asn1303Lys)", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:title]" }, "obj_type": { "value": "single nucleotide variant", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:obj_type]" }, "cdna_change": { "value": "c.3909C>A", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:variation_set[0].cdna_change]" }, "protein_change": { "value": "N1303K", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:protein_change]" }, "residue_position": { "value": 1303, "source": "[computed from protein_change]" }, "refseq_exon": { "exon_number": 24, "exon_label": "24/27", "exon_codon_span": "1293-1326", "near_splice_junction_le_3aa": false, "source": "[computed from RefSeq NM_000492.4 exon codon spans]" }, "structural_domain": { "domain_id": "NBD2_C_terminal", "name": "Nucleotide-Binding Domain 2 & C-terminal PDZ tail", "uniprot_ref": "UniProtKB:P13569:1191-1480", "pdb_refs": [ "5UAK", "6MSM", "8EIQ", "8EJ1" ], "structural_role": "Catalytic ATP hydrolysis site via NBD1:NBD2 head-to-tail dimerization; late cotranslational folding domain (N1303)." }, "cryoem_3d_coordinates": { "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.7, "dist_to_f508_in_6msm_angstrom": 35.56, "source": "[computed from RCSB PDB 6MSM, 5UAK, 8EIQ, 8EJ1 mmCIF C-alpha superposition]" }, "molecular_mechanism": { "consequence_class": "missense_snv", "canonical_cftr_class_note": "Missense substitution (may act via Class II folding, Class III gating, Class IV conductance, or VUS).", "source": "[computed from esummary:protein_change / HGVS missense]" }, "clinvar_classification": { "description": { "value": "Likely pathogenic", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.description]" }, "review_status": { "value": "criteria provided, single submitter", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.review_status]" }, "last_evaluated": { "value": "2025/08/03 00:00", "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:germline_classification.last_evaluated]" }, "supporting_scv_count": { "value": 1, "source": "[tools/variant_profile/fixtures/esummary_15_ids_trimmed.json:supporting_submissions.scv]" } }, "in_silico_annotations": { "fixture_source": "not stated", "cadd_phred": { "value": "not stated", "source": "[myvariant:cadd.phred]" }, "cadd_rawscore": { "value": "not stated", "source": "[myvariant:cadd.rawscore]" }, "grantham_distance": { "value": "not stated", "source": "[myvariant:cadd.grantham]" }, "exon": { "value": "not stated", "source": "[myvariant:cadd.exon]" }, "cadd_prot_domain": { "value": "not stated", "source": "[myvariant:cadd.gene.prot.domain]" }, "polyphen2_category": { "value": "not stated", "source": "[myvariant:cadd.polyphen.cat]" }, "polyphen2_score": { "value": "not stated", "source": "[myvariant:cadd.polyphen.val]" }, "sift_category": { "value": "not stated", "source": "[myvariant:cadd.sift.cat]" }, "sift_score": { "value": "not stated", "source": "[myvariant:cadd.sift.val]" } }, "predictor_concordance": { "status": "no_in_silico_fixture", "cadd_ge_20_deleterious": "not stated", "polyphen_damaging": "not stated", "sift_deleterious": "not stated", "predictor_agreement_note": "No offline MyVariant fixture recorded for this variation ID; sequence-conservation scores reported as 'not stated' rather than imputed." } } ], "uniprot_p13569_natural_variant_atlas": { "status": "verified_from_p13569_and_cryoem", "uniprot_accession": "P13569", "uniprot_entry_version": 286, "total_uniprot_natural_variants": 209, "single_residue_variants": 196, "multi_residue_variants": 13, "placed_in_6msm_cryoem_count": 191, "unplaced_disordered_region_count": 18, "near_exon_splice_junction_count": 17, "counts_by_domain": { "Lasso_N_terminal": 11, "TMD1": 54, "NBD1": 55, "R_domain": 15, "TMD2": 50, "NBD2_C_terminal": 24 }, "counts_by_exon": { "1/27": 1, "2/27": 6, "3/27": 7, "4/27": 15, "5/27": 5, "6/27": 8, "7/27": 2, "8/27": 21, "10/27": 4, "11/27": 13, "12/27": 10, "13/27": 17, "14/27": 26, "15/27": 2, "16/27": 6, "18/27": 10, "19/27": 4, "20/27": 22, "21/27": 6, "22/27": 2, "23/27": 14, "24/27": 2, "25/27": 3, "26/27": 1, "27/27": 2 }, "variants": [ { "uniprot_feature_id": "VAR_000101", "variant_label": "S13F", "start_aa": 13, "end_aa": 13, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "1/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.7, "delta_ca_6msm_vs_8eiq_angstrom": 0.59, "dist_to_f508_in_6msm_angstrom": 45.41, "dbsnp_ids": [ "rs397508635" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508635", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000102", "variant_label": "R31C", "start_aa": 31, "end_aa": 31, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 37.34, "dbsnp_ids": [ "rs1800073" ], "pubmed_count": 2, "uniprot_description": "in dbSNP:rs1800073", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000103", "variant_label": "R31L", "start_aa": 31, "end_aa": 31, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 37.34, "dbsnp_ids": [ "rs149353983" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs149353983", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000104", "variant_label": "S42F", "start_aa": 42, "end_aa": 42, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.55, "delta_ca_6msm_vs_8eiq_angstrom": 0.54, "dist_to_f508_in_6msm_angstrom": 28.57, "dbsnp_ids": [ "rs143456784" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs143456784", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000105", "variant_label": "D44G", "start_aa": 44, "end_aa": 44, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.29, "delta_ca_6msm_vs_8eiq_angstrom": 0.84, "dist_to_f508_in_6msm_angstrom": 28.71, "dbsnp_ids": [ "rs1800074" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs1800074", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000106", "variant_label": "D44V", "start_aa": 44, "end_aa": 44, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.29, "delta_ca_6msm_vs_8eiq_angstrom": 0.84, "dist_to_f508_in_6msm_angstrom": 28.71, "dbsnp_ids": [ "rs1800074" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs1800074", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000107", "variant_label": "S50Y", "start_aa": 50, "end_aa": 50, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "2/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.71, "delta_ca_6msm_vs_8eiq_angstrom": 0.3, "dist_to_f508_in_6msm_angstrom": 23.95, "dbsnp_ids": [ "rs397508220" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs397508220", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000108", "variant_label": "W57G", "start_aa": 57, "end_aa": 57, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "3/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.64, "delta_ca_6msm_vs_8eiq_angstrom": 0.56, "dist_to_f508_in_6msm_angstrom": 30.68, "dbsnp_ids": [ "rs397508272" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508272", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000109", "variant_label": "P67L", "start_aa": 67, "end_aa": 67, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "3/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.14, "delta_ca_6msm_vs_8eiq_angstrom": 0.85, "dist_to_f508_in_6msm_angstrom": 37.07, "dbsnp_ids": [ "rs368505753" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs368505753", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000110", "variant_label": "R74W", "start_aa": 74, "end_aa": 74, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "3/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.54, "delta_ca_6msm_vs_8eiq_angstrom": 0.35, "dist_to_f508_in_6msm_angstrom": 38.59, "dbsnp_ids": [ "rs115545701" ], "pubmed_count": 1, "uniprot_description": "in CF and CBAVD; uncertain significance; dbSNP:rs115545701", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000111", "variant_label": "R75Q", "start_aa": 75, "end_aa": 75, "span_type": "single_residue", "domain_id": "Lasso_N_terminal", "exon_label": "3/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.39, "delta_ca_6msm_vs_8eiq_angstrom": 0.46, "dist_to_f508_in_6msm_angstrom": 37.93, "dbsnp_ids": [ "rs1800076" ], "pubmed_count": 3, "uniprot_description": "in CF; dbSNP:rs1800076", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000112", "variant_label": "G85E", "start_aa": 85, "end_aa": 85, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "3/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.76, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 47.64, "dbsnp_ids": [ "rs75961395" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs75961395", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000113", "variant_label": "F87L", "start_aa": 87, "end_aa": 87, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "3/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.82, "delta_ca_6msm_vs_8eiq_angstrom": 0.41, "dist_to_f508_in_6msm_angstrom": 50.76, "dbsnp_ids": [ "rs397508403" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508403", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000114", "variant_label": "G91R", "start_aa": 91, "end_aa": 91, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "3/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.7, "delta_ca_6msm_vs_8eiq_angstrom": 0.32, "dist_to_f508_in_6msm_angstrom": 54.12, "dbsnp_ids": [ "rs121908750" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121908750", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000115", "variant_label": "E92K", "start_aa": 92, "end_aa": 92, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.37, "delta_ca_6msm_vs_8eiq_angstrom": 0.74, "dist_to_f508_in_6msm_angstrom": 55.1, "dbsnp_ids": [ "rs121908751" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs121908751", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000116", "variant_label": "Q98R", "start_aa": 98, "end_aa": 98, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.97, "delta_ca_6msm_vs_8eiq_angstrom": 0.55, "dist_to_f508_in_6msm_angstrom": 64.53, "dbsnp_ids": [ "rs397508464" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508464", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000118", "variant_label": "Y109C", "start_aa": 109, "end_aa": 109, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 2.88, "delta_ca_6msm_vs_8eiq_angstrom": 0.76, "dist_to_f508_in_6msm_angstrom": 79.54, "dbsnp_ids": [ "rs121909031" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909031", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000119", "variant_label": "D110H", "start_aa": 110, "end_aa": 110, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 2.88, "delta_ca_6msm_vs_8eiq_angstrom": 0.53, "dist_to_f508_in_6msm_angstrom": 82.38, "dbsnp_ids": [ "rs113993958" ], "pubmed_count": 2, "uniprot_description": "in CF and CBAVD; dbSNP:rs113993958", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000120", "variant_label": "P111L", "start_aa": 111, "end_aa": 111, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 4.04, "delta_ca_6msm_vs_8eiq_angstrom": 1.17, "dist_to_f508_in_6msm_angstrom": 85.89, "dbsnp_ids": [ "rs140502196" ], "pubmed_count": 0, "uniprot_description": "in CBAVD; dbSNP:rs140502196", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000121", "variant_label": "R117C", "start_aa": 117, "end_aa": 117, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "dbsnp_ids": [ "rs77834169" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs77834169", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000122", "variant_label": "R117H", "start_aa": 117, "end_aa": 117, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "dbsnp_ids": [ "rs78655421" ], "pubmed_count": 5, "uniprot_description": "in CF and CBAVD; strong decrease in single channel conductance; promotes rapid return to the closed state of the channel; decrease in bicarbonate transport; dbSNP:rs78655421", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000123", "variant_label": "R117L", "start_aa": 117, "end_aa": 117, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "dbsnp_ids": [ "rs78655421" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs78655421", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000124", "variant_label": "R117P", "start_aa": 117, "end_aa": 117, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 6.1, "delta_ca_6msm_vs_8eiq_angstrom": 0.39, "dist_to_f508_in_6msm_angstrom": 81.49, "dbsnp_ids": [ "rs78655421" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs78655421", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000125", "variant_label": "A120T", "start_aa": 120, "end_aa": 120, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.63, "delta_ca_6msm_vs_8eiq_angstrom": 0.94, "dist_to_f508_in_6msm_angstrom": 76.13, "dbsnp_ids": [ "rs201958172" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs201958172", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009895", "variant_label": "L138P", "start_aa": 138, "end_aa": 138, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.34, "delta_ca_6msm_vs_8eiq_angstrom": 0.3, "dist_to_f508_in_6msm_angstrom": 49.97, "dbsnp_ids": [ "rs1800078" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800078", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000126", "variant_label": "H139R", "start_aa": 139, "end_aa": 139, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.51, "delta_ca_6msm_vs_8eiq_angstrom": 0.42, "dist_to_f508_in_6msm_angstrom": 47.02, "dbsnp_ids": [ "rs76371115" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs76371115", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000127", "variant_label": "A141D", "start_aa": 141, "end_aa": 141, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.19, "delta_ca_6msm_vs_8eiq_angstrom": 0.64, "dist_to_f508_in_6msm_angstrom": 45.12, "dbsnp_ids": [ "rs397508700" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508700", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000128", "variant_label": "I148T", "start_aa": 148, "end_aa": 148, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.26, "delta_ca_6msm_vs_8eiq_angstrom": 0.28, "dist_to_f508_in_6msm_angstrom": 35.7, "dbsnp_ids": [ "rs35516286" ], "pubmed_count": 3, "uniprot_description": "in CF; uncertain significance; loss of bicarbonate transport; decreased inhibition of epithelial sodium channel (ENaC), when tested in a heterologous system; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity; dbSNP:rs35516286", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000129", "variant_label": "G149R", "start_aa": 149, "end_aa": 149, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "4/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.37, "delta_ca_6msm_vs_8eiq_angstrom": 0.29, "dist_to_f508_in_6msm_angstrom": 34.86, "dbsnp_ids": [ "rs397508718" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs397508718", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009896", "variant_label": "R170H", "start_aa": 170, "end_aa": 170, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "5/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.93, "delta_ca_6msm_vs_8eiq_angstrom": 0.82, "dist_to_f508_in_6msm_angstrom": 26.44, "dbsnp_ids": [ "rs1800079" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs1800079", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000130", "variant_label": "G178R", "start_aa": 178, "end_aa": 178, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "5/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.11, "delta_ca_6msm_vs_8eiq_angstrom": 0.5, "dist_to_f508_in_6msm_angstrom": 27.26, "dbsnp_ids": [ "rs80282562" ], "pubmed_count": 2, "uniprot_description": "in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity; dbSNP:rs80282562", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009897", "variant_label": "S182G", "start_aa": 182, "end_aa": 182, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "5/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.13, "delta_ca_6msm_vs_8eiq_angstrom": 0.41, "dist_to_f508_in_6msm_angstrom": 29.3, "dbsnp_ids": [ "rs1800080" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800080", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000131", "variant_label": "192del", "start_aa": 192, "end_aa": 192, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "5/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.69, "delta_ca_6msm_vs_8eiq_angstrom": 0.54, "dist_to_f508_in_6msm_angstrom": 35.07, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000132", "variant_label": "E193K", "start_aa": 193, "end_aa": 193, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "5/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.51, "delta_ca_6msm_vs_8eiq_angstrom": 0.77, "dist_to_f508_in_6msm_angstrom": 38.44, "dbsnp_ids": [ "rs397508759" ], "pubmed_count": 3, "uniprot_description": "in CBAVD and CF; decrease in bicarbonate transport; no effect on chloride channel activity; dbSNP:rs397508759", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000133", "variant_label": "H199Q", "start_aa": 199, "end_aa": 199, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.66, "delta_ca_6msm_vs_8eiq_angstrom": 0.53, "dist_to_f508_in_6msm_angstrom": 47.2, "dbsnp_ids": [ "rs397508765" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508765", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000134", "variant_label": "H199Y", "start_aa": 199, "end_aa": 199, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.66, "delta_ca_6msm_vs_8eiq_angstrom": 0.53, "dist_to_f508_in_6msm_angstrom": 47.2, "dbsnp_ids": [ "rs121908802" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121908802", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000135", "variant_label": "P205S", "start_aa": 205, "end_aa": 205, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.4, "delta_ca_6msm_vs_8eiq_angstrom": 0.31, "dist_to_f508_in_6msm_angstrom": 57.81, "dbsnp_ids": [ "rs121908803" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121908803", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000136", "variant_label": "L206W", "start_aa": 206, "end_aa": 206, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.91, "delta_ca_6msm_vs_8eiq_angstrom": 0.13, "dist_to_f508_in_6msm_angstrom": 58.94, "dbsnp_ids": [ "rs121908752" ], "pubmed_count": 2, "uniprot_description": "in CF and CBAVD; dbSNP:rs121908752", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080302", "variant_label": "220_1480del", "start_aa": 220, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.54, "delta_ca_6msm_vs_8eiq_angstrom": 0.91, "dist_to_f508_in_6msm_angstrom": 77.29, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000137", "variant_label": "C225R", "start_aa": 225, "end_aa": 225, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.19, "delta_ca_6msm_vs_8eiq_angstrom": 0.91, "dist_to_f508_in_6msm_angstrom": 72.66, "dbsnp_ids": [ "rs397508780" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs397508780", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080303", "variant_label": "V232D", "start_aa": 232, "end_aa": 232, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.72, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 64.01, "dbsnp_ids": [ "rs397508783" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs397508783", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000138", "variant_label": "M244K", "start_aa": 244, "end_aa": 244, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "6/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.95, "delta_ca_6msm_vs_8eiq_angstrom": 0.32, "dist_to_f508_in_6msm_angstrom": 47.82, "dbsnp_ids": [ "rs397508790" ], "pubmed_count": 0, "uniprot_description": "in CBAVD; dbSNP:rs397508790", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000139", "variant_label": "R258G", "start_aa": 258, "end_aa": 258, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "7/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.39, "delta_ca_6msm_vs_8eiq_angstrom": 0.51, "dist_to_f508_in_6msm_angstrom": 33.05, "dbsnp_ids": [ "rs191456345" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs191456345", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000140", "variant_label": "N287Y", "start_aa": 287, "end_aa": 287, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "7/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.97, "delta_ca_6msm_vs_8eiq_angstrom": 0.33, "dist_to_f508_in_6msm_angstrom": 42.14, "dbsnp_ids": [ "rs397508804" ], "pubmed_count": 2, "uniprot_description": "in CF; decreased presence at the cell membrane due to increased internalization from the apical cell membrane; no effect on single channel gating and conductance; dbSNP:rs397508804", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000141", "variant_label": "R297Q", "start_aa": 297, "end_aa": 297, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.13, "delta_ca_6msm_vs_8eiq_angstrom": 0.25, "dist_to_f508_in_6msm_angstrom": 48.29, "dbsnp_ids": [ "rs143486492" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs143486492", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000142", "variant_label": "Y301C", "start_aa": 301, "end_aa": 301, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.21, "delta_ca_6msm_vs_8eiq_angstrom": 0.4, "dist_to_f508_in_6msm_angstrom": 52.16, "dbsnp_ids": [ "rs150691494" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs150691494", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000143", "variant_label": "S307N", "start_aa": 307, "end_aa": 307, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.36, "delta_ca_6msm_vs_8eiq_angstrom": 0.44, "dist_to_f508_in_6msm_angstrom": 52.95, "dbsnp_ids": [ "rs397508817" ], "pubmed_count": 3, "uniprot_description": "in CBAVD and CF; dbSNP:rs397508817", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000144", "variant_label": "F311L", "start_aa": 311, "end_aa": 311, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.97, "delta_ca_6msm_vs_8eiq_angstrom": 0.27, "dist_to_f508_in_6msm_angstrom": 60.33, "dbsnp_ids": [ "rs121909016" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909016", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000145", "variant_label": "311del", "start_aa": 311, "end_aa": 311, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.97, "delta_ca_6msm_vs_8eiq_angstrom": 0.27, "dist_to_f508_in_6msm_angstrom": 60.33, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000146", "variant_label": "G314E", "start_aa": 314, "end_aa": 314, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.74, "delta_ca_6msm_vs_8eiq_angstrom": 0.58, "dist_to_f508_in_6msm_angstrom": 64.77, "dbsnp_ids": [ "rs75763344" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs75763344", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000147", "variant_label": "G314R", "start_aa": 314, "end_aa": 314, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.74, "delta_ca_6msm_vs_8eiq_angstrom": 0.58, "dist_to_f508_in_6msm_angstrom": 64.77, "dbsnp_ids": [ "rs397508819" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508819", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009898", "variant_label": "V322M", "start_aa": 322, "end_aa": 322, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.28, "delta_ca_6msm_vs_8eiq_angstrom": 0.6, "dist_to_f508_in_6msm_angstrom": 76.25, "dbsnp_ids": [ "rs1800085" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800085", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000148", "variant_label": "R334W", "start_aa": 334, "end_aa": 334, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.71, "delta_ca_6msm_vs_8eiq_angstrom": 0.56, "dist_to_f508_in_6msm_angstrom": 77.79, "dbsnp_ids": [ "rs121909011" ], "pubmed_count": 3, "uniprot_description": "in CF and CBAVD; mild; does not prevent maturation of glycans; dbSNP:rs121909011", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000150", "variant_label": "I336K", "start_aa": 336, "end_aa": 336, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.01, "delta_ca_6msm_vs_8eiq_angstrom": 0.58, "dist_to_f508_in_6msm_angstrom": 75.24, "dbsnp_ids": [ "rs397508139" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508139", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000151", "variant_label": "T338I", "start_aa": 338, "end_aa": 338, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.99, "delta_ca_6msm_vs_8eiq_angstrom": 0.6, "dist_to_f508_in_6msm_angstrom": 71.77, "dbsnp_ids": [ "rs77409459" ], "pubmed_count": 2, "uniprot_description": "in CF; mild; isolated hypotonic dehydration; dbSNP:rs77409459", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000152", "variant_label": "L346P", "start_aa": 346, "end_aa": 346, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.01, "delta_ca_6msm_vs_8eiq_angstrom": 0.59, "dist_to_f508_in_6msm_angstrom": 61.33, "dbsnp_ids": [ "rs397508146" ], "pubmed_count": 1, "uniprot_description": "in CF; dominant mutation but mild phenotype; dbSNP:rs397508146", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000153", "variant_label": "R347H", "start_aa": 347, "end_aa": 347, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.9, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 59.89, "dbsnp_ids": [ "rs77932196" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs77932196", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000154", "variant_label": "R347L", "start_aa": 347, "end_aa": 347, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.9, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 59.89, "dbsnp_ids": [ "rs77932196" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs77932196", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000155", "variant_label": "R347P", "start_aa": 347, "end_aa": 347, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 0.9, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 59.89, "dbsnp_ids": [ "rs77932196" ], "pubmed_count": 1, "uniprot_description": "in CF; mild; dbSNP:rs77932196", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009899", "variant_label": "T351S", "start_aa": 351, "end_aa": 351, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.38, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 56.34, "dbsnp_ids": [ "rs1800086" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800086", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000156", "variant_label": "R352Q", "start_aa": 352, "end_aa": 352, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.5, "delta_ca_6msm_vs_8eiq_angstrom": 0.59, "dist_to_f508_in_6msm_angstrom": 53.1, "dbsnp_ids": [ "rs121908753" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121908753", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009900", "variant_label": "Q353H", "start_aa": 353, "end_aa": 353, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.21, "delta_ca_6msm_vs_8eiq_angstrom": 0.26, "dist_to_f508_in_6msm_angstrom": 51.97, "dbsnp_ids": [ "rs1800087" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800087", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000158", "variant_label": "QT359_360KK", "start_aa": 359, "end_aa": 360, "span_type": "multi_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.27, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 45.59, "dbsnp_ids": [ "rs397508152" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508152", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000157", "variant_label": "Q359K", "start_aa": 359, "end_aa": 359, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.27, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 45.59, "dbsnp_ids": [ "rs76879328" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs76879328", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000159", "variant_label": "K370KNK", "start_aa": 370, "end_aa": 370, "span_type": "single_residue", "domain_id": "TMD1", "exon_label": "8/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.55, "delta_ca_6msm_vs_8eiq_angstrom": 0.66, "dist_to_f508_in_6msm_angstrom": 32.84, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080304", "variant_label": "D443Y", "start_aa": 443, "end_aa": 443, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "10/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.86, "delta_ca_6msm_vs_8eiq_angstrom": 1.06, "dist_to_f508_in_6msm_angstrom": 36.58, "dbsnp_ids": [ "rs147422190" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs147422190", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000160", "variant_label": "A455E", "start_aa": 455, "end_aa": 455, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "10/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.83, "delta_ca_6msm_vs_8eiq_angstrom": 1.71, "dist_to_f508_in_6msm_angstrom": 27.14, "dbsnp_ids": [ "rs74551128" ], "pubmed_count": 3, "uniprot_description": "in CF; dbSNP:rs74551128", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000161", "variant_label": "V456F", "start_aa": 456, "end_aa": 456, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "10/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.17, "delta_ca_6msm_vs_8eiq_angstrom": 2.11, "dist_to_f508_in_6msm_angstrom": 27.01, "dbsnp_ids": [ "rs397508195" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508195", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000162", "variant_label": "G458V", "start_aa": 458, "end_aa": 458, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "10/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.57, "delta_ca_6msm_vs_8eiq_angstrom": 1.8, "dist_to_f508_in_6msm_angstrom": 31.5, "dbsnp_ids": [ "rs121909009" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs121909009", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000163", "variant_label": "L467F", "start_aa": 467, "end_aa": 467, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.79, "delta_ca_6msm_vs_8eiq_angstrom": 1.56, "dist_to_f508_in_6msm_angstrom": 25.08, "dbsnp_ids": [ "rs1800089" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800089", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000164", "variant_label": "V470M", "start_aa": 470, "end_aa": 470, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.7, "delta_ca_6msm_vs_8eiq_angstrom": 1.47, "dist_to_f508_in_6msm_angstrom": 23.8, "dbsnp_ids": [ "rs213950" ], "pubmed_count": 7, "uniprot_description": "in dbSNP:rs213950", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000165", "variant_label": "G480C", "start_aa": 480, "end_aa": 480, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.7, "delta_ca_6msm_vs_8eiq_angstrom": 1.8, "dist_to_f508_in_6msm_angstrom": 33.23, "dbsnp_ids": [ "rs79282516" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs79282516", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000166", "variant_label": "S492F", "start_aa": 492, "end_aa": 492, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.55, "delta_ca_6msm_vs_8eiq_angstrom": 1.94, "dist_to_f508_in_6msm_angstrom": 15.18, "dbsnp_ids": [ "rs121909017" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909017", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000167", "variant_label": "E504Q", "start_aa": 504, "end_aa": 504, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.96, "delta_ca_6msm_vs_8eiq_angstrom": 2.4, "dist_to_f508_in_6msm_angstrom": 5.4, "dbsnp_ids": [ "rs397508223" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508223", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009901", "variant_label": "I506M", "start_aa": 506, "end_aa": 506, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.9, "delta_ca_6msm_vs_8eiq_angstrom": 2.02, "dist_to_f508_in_6msm_angstrom": 5.63, "dbsnp_ids": [ "rs1800092" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800092", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000168", "variant_label": "I506V", "start_aa": 506, "end_aa": 506, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.9, "delta_ca_6msm_vs_8eiq_angstrom": 2.02, "dist_to_f508_in_6msm_angstrom": 5.63, "dbsnp_ids": [ "rs1800091" ], "pubmed_count": 2, "uniprot_description": "in dbSNP:rs1800091", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000169", "variant_label": "I507V", "start_aa": 507, "end_aa": 507, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.68, "delta_ca_6msm_vs_8eiq_angstrom": 2.48, "dist_to_f508_in_6msm_angstrom": 3.86, "dbsnp_ids": [ "rs1801178" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1801178", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000170", "variant_label": "507del", "start_aa": 507, "end_aa": 507, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.68, "delta_ca_6msm_vs_8eiq_angstrom": 2.48, "dist_to_f508_in_6msm_angstrom": 3.86, "dbsnp_ids": [ "rs121908745" ], "pubmed_count": 2, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs121908745", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000172", "variant_label": "F508C", "start_aa": 508, "end_aa": 508, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK" ], "delta_ca_6msm_vs_5uak_angstrom": 9.19, "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": 0.0, "dbsnp_ids": [ "rs74571530" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs74571530", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000171", "variant_label": "508del", "start_aa": 508, "end_aa": 508, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK" ], "delta_ca_6msm_vs_5uak_angstrom": 9.19, "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": 0.0, "dbsnp_ids": [ "rs113993960" ], "pubmed_count": 20, "uniprot_description": "in CF and CBAVD; most common mutation in Caucasian CF chromosomes; impairs protein folding and stability; causes local changes to the surface that mediates interactions between domains; decreases frequency of channel opening in vitro; binds to the cytokeratin-8 and through this binding is primed for the degradation pathway that ends in the proteasome thus impairing trafficking; impairs maturation and trafficking to the cell membrane; impairs recycling to the cell membrane after endocytosis; abolishes MARCHF2-mediated degradation; dbSNP:rs121909001 and dbSNP:rs113993960", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000173", "variant_label": "D513G", "start_aa": 513, "end_aa": 513, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.32, "delta_ca_6msm_vs_8eiq_angstrom": 2.48, "dist_to_f508_in_6msm_angstrom": 12.33, "dbsnp_ids": [ "rs397508225" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs397508225", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000174", "variant_label": "V520F", "start_aa": 520, "end_aa": 520, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "11/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.65, "delta_ca_6msm_vs_8eiq_angstrom": 2.39, "dist_to_f508_in_6msm_angstrom": 13.86, "dbsnp_ids": [ "rs77646904" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs77646904", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_048150", "variant_label": "K532E", "start_aa": 532, "end_aa": 532, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.78, "delta_ca_6msm_vs_8eiq_angstrom": 1.78, "dist_to_f508_in_6msm_angstrom": 22.96, "dbsnp_ids": [ "rs35032490" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs35032490", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080305", "variant_label": "542_1480del", "start_aa": 542, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.47, "delta_ca_6msm_vs_8eiq_angstrom": 1.98, "dist_to_f508_in_6msm_angstrom": 15.8, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000175", "variant_label": "G544V", "start_aa": 544, "end_aa": 544, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.98, "delta_ca_6msm_vs_8eiq_angstrom": 1.0, "dist_to_f508_in_6msm_angstrom": 15.01, "dbsnp_ids": [ "rs397508241" ], "pubmed_count": 0, "uniprot_description": "in CBAVD; dbSNP:rs397508241", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000177", "variant_label": "S549I", "start_aa": 549, "end_aa": 549, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.36, "delta_ca_6msm_vs_8eiq_angstrom": 1.7, "dist_to_f508_in_6msm_angstrom": 20.35, "dbsnp_ids": [ "rs121908755" ], "pubmed_count": 3, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs121908755", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000176", "variant_label": "S549N", "start_aa": 549, "end_aa": 549, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.36, "delta_ca_6msm_vs_8eiq_angstrom": 1.7, "dist_to_f508_in_6msm_angstrom": 20.35, "dbsnp_ids": [ "rs121908755" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs121908755", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000178", "variant_label": "S549R", "start_aa": 549, "end_aa": 549, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.36, "delta_ca_6msm_vs_8eiq_angstrom": 1.7, "dist_to_f508_in_6msm_angstrom": 20.35, "dbsnp_ids": [ "rs121909005" ], "pubmed_count": 2, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs121909005", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000179", "variant_label": "G551D", "start_aa": 551, "end_aa": 551, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.39, "delta_ca_6msm_vs_8eiq_angstrom": 1.53, "dist_to_f508_in_6msm_angstrom": 19.46, "dbsnp_ids": [ "rs75527207" ], "pubmed_count": 10, "uniprot_description": "in CF; decrease in the frequency of channel opening in vitro; decrease in channel activity and ATPase activity; complete loss of bicarbonate transport; no effect on trafficking to the cell membrane; protein stability; nor on the maturation of glycans; dbSNP:rs75527207", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000180", "variant_label": "G551S", "start_aa": 551, "end_aa": 551, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.39, "delta_ca_6msm_vs_8eiq_angstrom": 1.53, "dist_to_f508_in_6msm_angstrom": 19.46, "dbsnp_ids": [ "rs121909013" ], "pubmed_count": 1, "uniprot_description": "in CF; decrease in bicarbonate transport; no effect on chloride channel activity; dbSNP:rs121909013", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000181", "variant_label": "R553Q", "start_aa": 553, "end_aa": 553, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.98, "delta_ca_6msm_vs_8eiq_angstrom": 1.67, "dist_to_f508_in_6msm_angstrom": 14.49, "dbsnp_ids": [ "rs121909044" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909044", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080306", "variant_label": "I556V", "start_aa": 556, "end_aa": 556, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "12/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.94, "delta_ca_6msm_vs_8eiq_angstrom": 1.75, "dist_to_f508_in_6msm_angstrom": 11.03, "dbsnp_ids": [ "rs75789129" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs75789129", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000182", "variant_label": "L558S", "start_aa": 558, "end_aa": 558, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.24, "delta_ca_6msm_vs_8eiq_angstrom": 1.84, "dist_to_f508_in_6msm_angstrom": 12.27, "dbsnp_ids": [ "rs193922504" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs193922504", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000183", "variant_label": "A559T", "start_aa": 559, "end_aa": 559, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.99, "delta_ca_6msm_vs_8eiq_angstrom": 2.25, "dist_to_f508_in_6msm_angstrom": 10.37, "dbsnp_ids": [ "rs75549581" ], "pubmed_count": 2, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs75549581", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000184", "variant_label": "R560K", "start_aa": 560, "end_aa": 560, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.82, "delta_ca_6msm_vs_8eiq_angstrom": 2.2, "dist_to_f508_in_6msm_angstrom": 6.99, "dbsnp_ids": [ "rs80055610" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs80055610", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000185", "variant_label": "R560S", "start_aa": 560, "end_aa": 560, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.82, "delta_ca_6msm_vs_8eiq_angstrom": 2.2, "dist_to_f508_in_6msm_angstrom": 6.99, "dbsnp_ids": [ "rs397508267" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508267", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000186", "variant_label": "R560T", "start_aa": 560, "end_aa": 560, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.82, "delta_ca_6msm_vs_8eiq_angstrom": 2.2, "dist_to_f508_in_6msm_angstrom": 6.99, "dbsnp_ids": [ "rs80055610" ], "pubmed_count": 2, "uniprot_description": "in CF; impairs maturation and trafficking to the cell membrane; decrease in channel activity; dbSNP:rs80055610", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080307", "variant_label": "A561E", "start_aa": 561, "end_aa": 561, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.01, "delta_ca_6msm_vs_8eiq_angstrom": 1.96, "dist_to_f508_in_6msm_angstrom": 9.68, "dbsnp_ids": [ "rs121909047" ], "pubmed_count": 1, "uniprot_description": "in CF; impairs maturation and trafficking to the cell membrane; decrease in channel activity; dbSNP:rs121909047", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000187", "variant_label": "V562I", "start_aa": 562, "end_aa": 562, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.31, "delta_ca_6msm_vs_8eiq_angstrom": 2.4, "dist_to_f508_in_6msm_angstrom": 11.48, "dbsnp_ids": [ "rs1800097" ], "pubmed_count": 4, "uniprot_description": "in CBAVD and CF; uncertain significance; found in cis of the IVS8 TG11-T5 allele which affects exon 9 splicing; no effect on protein maturation; trafficking to the cell membrane; nor on channel activity; dbSNP:rs1800097", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000188", "variant_label": "V562L", "start_aa": 562, "end_aa": 562, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.31, "delta_ca_6msm_vs_8eiq_angstrom": 2.4, "dist_to_f508_in_6msm_angstrom": 11.48, "dbsnp_ids": [ "rs1800097" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs1800097", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000189", "variant_label": "Y563N", "start_aa": 563, "end_aa": 563, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.86, "delta_ca_6msm_vs_8eiq_angstrom": 2.52, "dist_to_f508_in_6msm_angstrom": 9.03, "dbsnp_ids": [ "rs121909006" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs121909006", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000190", "variant_label": "Y569C", "start_aa": 569, "end_aa": 569, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.19, "delta_ca_6msm_vs_8eiq_angstrom": 2.36, "dist_to_f508_in_6msm_angstrom": 15.92, "dbsnp_ids": [ "rs397508277" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508277", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000191", "variant_label": "Y569D", "start_aa": 569, "end_aa": 569, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.19, "delta_ca_6msm_vs_8eiq_angstrom": 2.36, "dist_to_f508_in_6msm_angstrom": 15.92, "dbsnp_ids": [ "rs397508276" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508276", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000192", "variant_label": "Y569H", "start_aa": 569, "end_aa": 569, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.19, "delta_ca_6msm_vs_8eiq_angstrom": 2.36, "dist_to_f508_in_6msm_angstrom": 15.92, "dbsnp_ids": [ "rs397508276" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs397508276", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000193", "variant_label": "L571S", "start_aa": 571, "end_aa": 571, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.43, "delta_ca_6msm_vs_8eiq_angstrom": 1.9, "dist_to_f508_in_6msm_angstrom": 17.37, "dbsnp_ids": [ "rs397508280" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508280", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000194", "variant_label": "D572N", "start_aa": 572, "end_aa": 572, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.76, "delta_ca_6msm_vs_8eiq_angstrom": 1.83, "dist_to_f508_in_6msm_angstrom": 19.04, "dbsnp_ids": [ "rs397508282" ], "pubmed_count": 2, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508282", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000195", "variant_label": "P574H", "start_aa": 574, "end_aa": 574, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.51, "delta_ca_6msm_vs_8eiq_angstrom": 2.02, "dist_to_f508_in_6msm_angstrom": 18.51, "dbsnp_ids": [ "rs121908758" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs121908758", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000196", "variant_label": "G576A", "start_aa": 576, "end_aa": 576, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.36, "delta_ca_6msm_vs_8eiq_angstrom": 1.2, "dist_to_f508_in_6msm_angstrom": 23.24, "dbsnp_ids": [ "rs1800098" ], "pubmed_count": 2, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs1800098", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000197", "variant_label": "D579G", "start_aa": 579, "end_aa": 579, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "13/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.78, "delta_ca_6msm_vs_8eiq_angstrom": 1.67, "dist_to_f508_in_6msm_angstrom": 26.71, "dbsnp_ids": [ "rs397508288" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs397508288", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000198", "variant_label": "I601F", "start_aa": 601, "end_aa": 601, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.3, "delta_ca_6msm_vs_8eiq_angstrom": 1.81, "dist_to_f508_in_6msm_angstrom": 21.97, "dbsnp_ids": [ "rs397508306" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508306", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_048151", "variant_label": "S605F", "start_aa": 605, "end_aa": 605, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.03, "delta_ca_6msm_vs_8eiq_angstrom": 1.62, "dist_to_f508_in_6msm_angstrom": 29.37, "dbsnp_ids": [ "rs766874" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs766874", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000199", "variant_label": "L610S", "start_aa": 610, "end_aa": 610, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.55, "delta_ca_6msm_vs_8eiq_angstrom": 2.1, "dist_to_f508_in_6msm_angstrom": 30.98, "dbsnp_ids": [ "rs397508311" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508311", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000200", "variant_label": "A613T", "start_aa": 613, "end_aa": 613, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.56, "delta_ca_6msm_vs_8eiq_angstrom": 2.58, "dist_to_f508_in_6msm_angstrom": 29.12, "dbsnp_ids": [ "rs201978662" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs201978662", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000201", "variant_label": "D614G", "start_aa": 614, "end_aa": 614, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.21, "delta_ca_6msm_vs_8eiq_angstrom": 2.35, "dist_to_f508_in_6msm_angstrom": 30.87, "dbsnp_ids": [ "rs201124247" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs201124247", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000202", "variant_label": "I618T", "start_aa": 618, "end_aa": 618, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.16, "delta_ca_6msm_vs_8eiq_angstrom": 1.99, "dist_to_f508_in_6msm_angstrom": 32.94, "dbsnp_ids": [ "rs139468767" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs139468767", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000203", "variant_label": "L619S", "start_aa": 619, "end_aa": 619, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.95, "delta_ca_6msm_vs_8eiq_angstrom": 1.9, "dist_to_f508_in_6msm_angstrom": 32.63, "dbsnp_ids": [ "rs397508313" ], "pubmed_count": 2, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508313", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000204", "variant_label": "H620P", "start_aa": 620, "end_aa": 620, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.15, "delta_ca_6msm_vs_8eiq_angstrom": 1.81, "dist_to_f508_in_6msm_angstrom": 35.18, "dbsnp_ids": [ "rs397508314" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508314", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000205", "variant_label": "H620Q", "start_aa": 620, "end_aa": 620, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.15, "delta_ca_6msm_vs_8eiq_angstrom": 1.81, "dist_to_f508_in_6msm_angstrom": 35.18, "dbsnp_ids": [ "rs397508315" ], "pubmed_count": 1, "uniprot_description": "in CF; strong decrease in bicarbonate transport; increase in chloride channel activity in vitro; no effect on glycan maturation; dbSNP:rs397508315", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000206", "variant_label": "G622D", "start_aa": 622, "end_aa": 622, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.68, "delta_ca_6msm_vs_8eiq_angstrom": 1.56, "dist_to_f508_in_6msm_angstrom": 33.71, "dbsnp_ids": [ "rs121908759" ], "pubmed_count": 2, "uniprot_description": "in CBAVD; decreased channel activity; has no effect on glycan maturation; dbSNP:rs121908759", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000207", "variant_label": "G628R", "start_aa": 628, "end_aa": 628, "span_type": "single_residue", "domain_id": "NBD1", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.91, "delta_ca_6msm_vs_8eiq_angstrom": 2.38, "dist_to_f508_in_6msm_angstrom": 35.87, "dbsnp_ids": [ "rs397508316" ], "pubmed_count": 3, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508316", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000208", "variant_label": "L633P", "start_aa": 633, "end_aa": 633, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.93, "delta_ca_6msm_vs_8eiq_angstrom": 2.12, "dist_to_f508_in_6msm_angstrom": 39.85, "dbsnp_ids": [ "rs397508318" ], "pubmed_count": 1, "uniprot_description": "in CF; impaired maturation of glycan chains; dbSNP:rs397508318", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000209", "variant_label": "D648V", "start_aa": 648, "end_aa": 648, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs121909033" ], "pubmed_count": 1, "uniprot_description": "in CF; decrease in bicarbonate transport; no effect chloride channel activity; dbSNP:rs121909033", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000210", "variant_label": "D651N", "start_aa": 651, "end_aa": 651, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs780526529" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs780526529", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009902", "variant_label": "S654G", "start_aa": 654, "end_aa": 654, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs1800099" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800099", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000211", "variant_label": "T665S", "start_aa": 665, "end_aa": 665, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs1177201180" ], "pubmed_count": 2, "uniprot_description": "in CF; uncertain significance; no effect on glycan maturation and channel activity; dbSNP:rs1177201180", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000212", "variant_label": "R668C", "start_aa": 668, "end_aa": 668, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs1800100" ], "pubmed_count": 3, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs1800100", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000213", "variant_label": "F693L", "start_aa": 693, "end_aa": 693, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs397508338" ], "pubmed_count": 3, "uniprot_description": "in CF; uncertain significance; no effect on glycan maturation; no effect on channel activity; dbSNP:rs145540754 and dbSNP:rs397508338", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080308", "variant_label": "710_1480del", "start_aa": 710, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000214", "variant_label": "V754M", "start_aa": 754, "end_aa": 754, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs150157202" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs150157202", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000215", "variant_label": "R766M", "start_aa": 766, "end_aa": 766, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs397508363" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; no effect on glycan maturation; no effect on channel activity; dbSNP:rs397508363", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000216", "variant_label": "R792G", "start_aa": 792, "end_aa": 792, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs145449046" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; no effect on glycan maturation but decreased channel activity; dbSNP:rs145449046", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000217", "variant_label": "A800G", "start_aa": 800, "end_aa": 800, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs397508373" ], "pubmed_count": 3, "uniprot_description": "in CBAVD; small decrease in bicarbonate transport; increase in chloride channel activity in vitro; no effect on glycan maturation; dbSNP:rs397508373", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000218", "variant_label": "I807M", "start_aa": 807, "end_aa": 807, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs1800103" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; no effect on glycan maturation; no effect on channel activity; dbSNP:rs1800103", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000219", "variant_label": "E822K", "start_aa": 822, "end_aa": 822, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs397508378" ], "pubmed_count": 1, "uniprot_description": "in CF; no effect on glycan maturation but decreased channel activity; dbSNP:rs397508378", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000220", "variant_label": "E826K", "start_aa": 826, "end_aa": 826, "span_type": "single_residue", "domain_id": "R_domain", "exon_label": "14/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs397508381" ], "pubmed_count": 1, "uniprot_description": "in thoracic sarcoidosis; uncertain significance; no effect on glycan maturation and channel activity; dbSNP:rs397508381", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080309", "variant_label": "846_1480del", "start_aa": 846, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "15/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.06, "delta_ca_6msm_vs_8eiq_angstrom": 0.63, "dist_to_f508_in_6msm_angstrom": 48.02, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000221", "variant_label": "C866Y", "start_aa": 866, "end_aa": 866, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "15/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.2, "delta_ca_6msm_vs_8eiq_angstrom": 0.17, "dist_to_f508_in_6msm_angstrom": 61.38, "dbsnp_ids": [ "rs193922506" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs193922506", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080310", "variant_label": "890_1480del", "start_aa": 890, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [], "pubmed_count": 2, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009903", "variant_label": "Y903H", "start_aa": 903, "end_aa": 903, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": 3.97, "dist_to_f508_in_6msm_angstrom": 85.89, "dbsnp_ids": [ "rs1800106" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800106", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009904", "variant_label": "S909I", "start_aa": 909, "end_aa": 909, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": 18.97, "delta_ca_6msm_vs_8eiq_angstrom": 3.98, "dist_to_f508_in_6msm_angstrom": 85.24, "dbsnp_ids": [ "rs1800107" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800107", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000222", "variant_label": "S912L", "start_aa": 912, "end_aa": 912, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 15.88, "delta_ca_6msm_vs_8eiq_angstrom": 3.08, "dist_to_f508_in_6msm_angstrom": 80.85, "dbsnp_ids": [ "rs121909034" ], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance; dbSNP:rs121909034", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000223", "variant_label": "Y913C", "start_aa": 913, "end_aa": 913, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 14.11, "delta_ca_6msm_vs_8eiq_angstrom": 1.97, "dist_to_f508_in_6msm_angstrom": 77.74, "dbsnp_ids": [ "rs121909008" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909008", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000224", "variant_label": "Y917C", "start_aa": 917, "end_aa": 917, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "16/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.01, "delta_ca_6msm_vs_8eiq_angstrom": 0.78, "dist_to_f508_in_6msm_angstrom": 71.9, "dbsnp_ids": [ "rs397508428" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508428", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080311", "variant_label": "V938G", "start_aa": 938, "end_aa": 938, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.42, "delta_ca_6msm_vs_8eiq_angstrom": 0.31, "dist_to_f508_in_6msm_angstrom": 51.1, "dbsnp_ids": [ "rs193922511" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs193922511", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000225", "variant_label": "H949Y", "start_aa": 949, "end_aa": 949, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.56, "delta_ca_6msm_vs_8eiq_angstrom": 0.42, "dist_to_f508_in_6msm_angstrom": 38.64, "dbsnp_ids": [ "rs121909035" ], "pubmed_count": 2, "uniprot_description": "in CF; decrease in bicarbonate transport; no effect on chloride channel activity; dbSNP:rs121909035", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000226", "variant_label": "M952I", "start_aa": 952, "end_aa": 952, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.72, "delta_ca_6msm_vs_8eiq_angstrom": 0.32, "dist_to_f508_in_6msm_angstrom": 36.67, "dbsnp_ids": [ "rs151048781" ], "pubmed_count": 2, "uniprot_description": "in CF and CBAVD; uncertain significance; dbSNP:rs151048781", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080312", "variant_label": "A959V", "start_aa": 959, "end_aa": 959, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.64, "delta_ca_6msm_vs_8eiq_angstrom": 0.84, "dist_to_f508_in_6msm_angstrom": 34.11, "dbsnp_ids": [ "rs397508448" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs397508448", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_009905", "variant_label": "L967S", "start_aa": 967, "end_aa": 967, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.74, "delta_ca_6msm_vs_8eiq_angstrom": 1.14, "dist_to_f508_in_6msm_angstrom": 23.67, "dbsnp_ids": [ "rs1800110" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs1800110", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080313", "variant_label": "S977F", "start_aa": 977, "end_aa": 977, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.12, "delta_ca_6msm_vs_8eiq_angstrom": 0.36, "dist_to_f508_in_6msm_angstrom": 30.38, "dbsnp_ids": [ "rs141033578" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs141033578", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000227", "variant_label": "L997F", "start_aa": 997, "end_aa": 997, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.49, "delta_ca_6msm_vs_8eiq_angstrom": 0.26, "dist_to_f508_in_6msm_angstrom": 56.45, "dbsnp_ids": [ "rs1800111" ], "pubmed_count": 1, "uniprot_description": "in CF and CBAVD; uncertain significance; dbSNP:rs1800111", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000228", "variant_label": "I1005R", "start_aa": 1005, "end_aa": 1005, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.25, "delta_ca_6msm_vs_8eiq_angstrom": 0.6, "dist_to_f508_in_6msm_angstrom": 66.71, "dbsnp_ids": [ "rs397508479" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508479", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000229", "variant_label": "A1006E", "start_aa": 1006, "end_aa": 1006, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.88, "delta_ca_6msm_vs_8eiq_angstrom": 0.69, "dist_to_f508_in_6msm_angstrom": 68.59, "dbsnp_ids": [ "rs397508480" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs397508480", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000230", "variant_label": "P1013L", "start_aa": 1013, "end_aa": 1013, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "18/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.15, "delta_ca_6msm_vs_8eiq_angstrom": 0.37, "dist_to_f508_in_6msm_angstrom": 75.21, "dbsnp_ids": [ "rs193922516" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs193922516", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080314", "variant_label": "1023_1024del", "start_aa": 1023, "end_aa": 1024, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "19/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.91, "delta_ca_6msm_vs_8eiq_angstrom": 0.37, "dist_to_f508_in_6msm_angstrom": 59.74, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080315", "variant_label": "I1027T", "start_aa": 1027, "end_aa": 1027, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "19/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.77, "delta_ca_6msm_vs_8eiq_angstrom": 0.36, "dist_to_f508_in_6msm_angstrom": 53.94, "dbsnp_ids": [ "rs1800112" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs1800112", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000231", "variant_label": "M1028I", "start_aa": 1028, "end_aa": 1028, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "19/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.08, "delta_ca_6msm_vs_8eiq_angstrom": 0.47, "dist_to_f508_in_6msm_angstrom": 53.56, "dbsnp_ids": [ "rs200553511" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs200553511", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080316", "variant_label": "Y1032C", "start_aa": 1032, "end_aa": 1032, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "19/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.3, "delta_ca_6msm_vs_8eiq_angstrom": 0.37, "dist_to_f508_in_6msm_angstrom": 47.37, "dbsnp_ids": [ "rs144055758" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs144055758", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000232", "variant_label": "F1052V", "start_aa": 1052, "end_aa": 1052, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.28, "delta_ca_6msm_vs_8eiq_angstrom": 0.41, "dist_to_f508_in_6msm_angstrom": 20.45, "dbsnp_ids": [ "rs150212784" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs150212784", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000233", "variant_label": "G1061R", "start_aa": 1061, "end_aa": 1061, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.21, "delta_ca_6msm_vs_8eiq_angstrom": 0.97, "dist_to_f508_in_6msm_angstrom": 12.89, "dbsnp_ids": [ "rs142394380" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs142394380", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080317", "variant_label": "1063_1480del", "start_aa": 1063, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.29, "delta_ca_6msm_vs_8eiq_angstrom": 0.8, "dist_to_f508_in_6msm_angstrom": 14.22, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000234", "variant_label": "L1065P", "start_aa": 1065, "end_aa": 1065, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.31, "delta_ca_6msm_vs_8eiq_angstrom": 0.97, "dist_to_f508_in_6msm_angstrom": 9.69, "dbsnp_ids": [ "rs121909036" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909036", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000235", "variant_label": "L1065R", "start_aa": 1065, "end_aa": 1065, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.31, "delta_ca_6msm_vs_8eiq_angstrom": 0.97, "dist_to_f508_in_6msm_angstrom": 9.69, "dbsnp_ids": [ "rs121909036" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909036", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000236", "variant_label": "R1066C", "start_aa": 1066, "end_aa": 1066, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.26, "delta_ca_6msm_vs_8eiq_angstrom": 0.78, "dist_to_f508_in_6msm_angstrom": 12.64, "dbsnp_ids": [ "rs78194216" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs78194216", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000237", "variant_label": "R1066H", "start_aa": 1066, "end_aa": 1066, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.26, "delta_ca_6msm_vs_8eiq_angstrom": 0.78, "dist_to_f508_in_6msm_angstrom": 12.64, "dbsnp_ids": [ "rs121909019" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909019", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000238", "variant_label": "R1066L", "start_aa": 1066, "end_aa": 1066, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.26, "delta_ca_6msm_vs_8eiq_angstrom": 0.78, "dist_to_f508_in_6msm_angstrom": 12.64, "dbsnp_ids": [ "rs121909019" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909019", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000239", "variant_label": "A1067T", "start_aa": 1067, "end_aa": 1067, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.48, "delta_ca_6msm_vs_8eiq_angstrom": 0.81, "dist_to_f508_in_6msm_angstrom": 12.1, "dbsnp_ids": [ "rs121909020" ], "pubmed_count": 1, "uniprot_description": "in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane nor on chloride channel activity; dbSNP:rs121909020", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000240", "variant_label": "A1067V", "start_aa": 1067, "end_aa": 1067, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 9.48, "delta_ca_6msm_vs_8eiq_angstrom": 0.81, "dist_to_f508_in_6msm_angstrom": 12.1, "dbsnp_ids": [ "rs1800114" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs1800114", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080318", "variant_label": "G1069R", "start_aa": 1069, "end_aa": 1069, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.43, "delta_ca_6msm_vs_8eiq_angstrom": 1.13, "dist_to_f508_in_6msm_angstrom": 10.51, "dbsnp_ids": [ "rs200321110" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs200321110", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000242", "variant_label": "R1070P", "start_aa": 1070, "end_aa": 1070, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.19, "delta_ca_6msm_vs_8eiq_angstrom": 1.28, "dist_to_f508_in_6msm_angstrom": 8.21, "dbsnp_ids": [ "rs78769542" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs78769542", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000241", "variant_label": "R1070Q", "start_aa": 1070, "end_aa": 1070, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.19, "delta_ca_6msm_vs_8eiq_angstrom": 1.28, "dist_to_f508_in_6msm_angstrom": 8.21, "dbsnp_ids": [ "rs78769542" ], "pubmed_count": 2, "uniprot_description": "in CF; decrease in bicarbonate transport; no effect on chloride channel activity; dbSNP:rs78769542", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_011564", "variant_label": "R1070W", "start_aa": 1070, "end_aa": 1070, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.19, "delta_ca_6msm_vs_8eiq_angstrom": 1.28, "dist_to_f508_in_6msm_angstrom": 8.21, "dbsnp_ids": [ "rs202179988" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; dbSNP:rs202179988", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000243", "variant_label": "Q1071P", "start_aa": 1071, "end_aa": 1071, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.71, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 11.37, "dbsnp_ids": [ "rs121909037" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909037", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000244", "variant_label": "P1072L", "start_aa": 1072, "end_aa": 1072, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.21, "delta_ca_6msm_vs_8eiq_angstrom": 1.12, "dist_to_f508_in_6msm_angstrom": 11.87, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000245", "variant_label": "L1077P", "start_aa": 1077, "end_aa": 1077, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.53, "delta_ca_6msm_vs_8eiq_angstrom": 0.58, "dist_to_f508_in_6msm_angstrom": 12.09, "dbsnp_ids": [ "rs139304906" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs139304906", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000246", "variant_label": "H1085R", "start_aa": 1085, "end_aa": 1085, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.51, "delta_ca_6msm_vs_8eiq_angstrom": 0.5, "dist_to_f508_in_6msm_angstrom": 24.76, "dbsnp_ids": [ "rs79635528" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs79635528", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080319", "variant_label": "1092_1480del", "start_aa": 1092, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.96, "delta_ca_6msm_vs_8eiq_angstrom": 0.44, "dist_to_f508_in_6msm_angstrom": 35.17, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000247", "variant_label": "W1098R", "start_aa": 1098, "end_aa": 1098, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.15, "delta_ca_6msm_vs_8eiq_angstrom": 0.47, "dist_to_f508_in_6msm_angstrom": 44.64, "dbsnp_ids": [ "rs397508531" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508531", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000248", "variant_label": "M1101K", "start_aa": 1101, "end_aa": 1101, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.37, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 49.01, "dbsnp_ids": [ "rs36210737" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs36210737", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_011565", "variant_label": "M1101R", "start_aa": 1101, "end_aa": 1101, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "20/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 1.37, "delta_ca_6msm_vs_8eiq_angstrom": 0.38, "dist_to_f508_in_6msm_angstrom": 49.01, "dbsnp_ids": [ "rs36210737" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs36210737", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000249", "variant_label": "M1137V", "start_aa": 1137, "end_aa": 1137, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.9, "delta_ca_6msm_vs_8eiq_angstrom": 0.58, "dist_to_f508_in_6msm_angstrom": 64.8, "dbsnp_ids": [ "rs397508553" ], "pubmed_count": 1, "uniprot_description": "in CF; decreases channel activity; no visible effect on protein maturation; dbSNP:rs397508553", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000250", "variant_label": "1140del", "start_aa": 1140, "end_aa": 1140, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 5.66, "delta_ca_6msm_vs_8eiq_angstrom": 0.56, "dist_to_f508_in_6msm_angstrom": 60.67, "dbsnp_ids": [ "rs397508557" ], "pubmed_count": 2, "uniprot_description": "in CF; abolishes channel activity; no visible effect on protein maturation; dbSNP:rs397508557", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000251", "variant_label": "D1152H", "start_aa": 1152, "end_aa": 1152, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 3.06, "delta_ca_6msm_vs_8eiq_angstrom": 0.46, "dist_to_f508_in_6msm_angstrom": 43.57, "dbsnp_ids": [ "rs75541969" ], "pubmed_count": 2, "uniprot_description": "in CF and CBAVD; decreases channel activity; no visible effect on protein maturation; dbSNP:rs75541969", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080320", "variant_label": "V1153E", "start_aa": 1153, "end_aa": 1153, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 2.29, "delta_ca_6msm_vs_8eiq_angstrom": 0.46, "dist_to_f508_in_6msm_angstrom": 44.54, "dbsnp_ids": [ "rs397508567" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs397508567", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080321", "variant_label": "1162_1480del", "start_aa": 1162, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.67, "delta_ca_6msm_vs_8eiq_angstrom": 0.48, "dist_to_f508_in_6msm_angstrom": 34.48, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000252", "variant_label": "R1162L", "start_aa": 1162, "end_aa": 1162, "span_type": "single_residue", "domain_id": "TMD2", "exon_label": "21/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 4.67, "delta_ca_6msm_vs_8eiq_angstrom": 0.48, "dist_to_f508_in_6msm_angstrom": 34.48, "dbsnp_ids": [ "rs1800120" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs1800120", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080322", "variant_label": "K1200E", "start_aa": 1200, "end_aa": 1200, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "22/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF; uncertain significance", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080323", "variant_label": "1204_1480del", "start_aa": 1204, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "NBD2_C_terminal", "exon_label": "22/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "8EIQ" ], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": 1.21, "dist_to_f508_in_6msm_angstrom": 52.28, "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CF", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000253", "variant_label": "T1220I", "start_aa": 1220, "end_aa": 1220, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.98, "delta_ca_6msm_vs_8eiq_angstrom": 1.47, "dist_to_f508_in_6msm_angstrom": 28.37, "dbsnp_ids": [ "rs1800123" ], "pubmed_count": 1, "uniprot_description": "in dbSNP:rs1800123", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000254", "variant_label": "I1234V", "start_aa": 1234, "end_aa": 1234, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.92, "delta_ca_6msm_vs_8eiq_angstrom": 0.78, "dist_to_f508_in_6msm_angstrom": 46.32, "dbsnp_ids": [ "rs75389940" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs75389940", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000255", "variant_label": "S1235R", "start_aa": 1235, "end_aa": 1235, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.77, "delta_ca_6msm_vs_8eiq_angstrom": 0.7, "dist_to_f508_in_6msm_angstrom": 49.75, "dbsnp_ids": [ "rs34911792" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs34911792", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000256", "variant_label": "G1244E", "start_aa": 1244, "end_aa": 1244, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 10.8, "delta_ca_6msm_vs_8eiq_angstrom": 1.39, "dist_to_f508_in_6msm_angstrom": 30.57, "dbsnp_ids": [ "rs267606723" ], "pubmed_count": 1, "uniprot_description": "in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity; dbSNP:rs267606723", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000257", "variant_label": "G1249E", "start_aa": 1249, "end_aa": 1249, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.59, "delta_ca_6msm_vs_8eiq_angstrom": 1.57, "dist_to_f508_in_6msm_angstrom": 27.94, "dbsnp_ids": [ "rs121909040" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909040", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000258", "variant_label": "S1251N", "start_aa": 1251, "end_aa": 1251, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.67, "delta_ca_6msm_vs_8eiq_angstrom": 1.3, "dist_to_f508_in_6msm_angstrom": 28.53, "dbsnp_ids": [ "rs74503330" ], "pubmed_count": 2, "uniprot_description": "in CF; dbSNP:rs74503330", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000259", "variant_label": "S1255P", "start_aa": 1255, "end_aa": 1255, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.35, "delta_ca_6msm_vs_8eiq_angstrom": 0.96, "dist_to_f508_in_6msm_angstrom": 31.96, "dbsnp_ids": [ "rs121909041" ], "pubmed_count": 2, "uniprot_description": "in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity; dbSNP:rs121909041", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000260", "variant_label": "D1270N", "start_aa": 1270, "end_aa": 1270, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.94, "delta_ca_6msm_vs_8eiq_angstrom": 1.01, "dist_to_f508_in_6msm_angstrom": 51.48, "dbsnp_ids": [ "rs11971167" ], "pubmed_count": 1, "uniprot_description": "in CF and CBAVD; dbSNP:rs11971167", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080324", "variant_label": "1282_1480del", "start_aa": 1282, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 43.8, "dbsnp_ids": [], "pubmed_count": 2, "uniprot_description": "in CF and CBAVD", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000261", "variant_label": "W1282R", "start_aa": 1282, "end_aa": 1282, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 6.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.43, "dist_to_f508_in_6msm_angstrom": 43.8, "dbsnp_ids": [ "rs397508616" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508616", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000262", "variant_label": "R1283M", "start_aa": 1283, "end_aa": 1283, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.36, "delta_ca_6msm_vs_8eiq_angstrom": 1.12, "dist_to_f508_in_6msm_angstrom": 40.61, "dbsnp_ids": [ "rs77902683" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs77902683", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000263", "variant_label": "F1286S", "start_aa": 1286, "end_aa": 1286, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 7.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.88, "dist_to_f508_in_6msm_angstrom": 40.73, "dbsnp_ids": [ "rs121909028" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909028", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000264", "variant_label": "Q1291H", "start_aa": 1291, "end_aa": 1291, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.72, "delta_ca_6msm_vs_8eiq_angstrom": 1.1, "dist_to_f508_in_6msm_angstrom": 26.16, "dbsnp_ids": [ "rs121909015" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909015", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000265", "variant_label": "Q1291R", "start_aa": 1291, "end_aa": 1291, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "23/27", "near_splice_junction_le_3aa": true, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.72, "delta_ca_6msm_vs_8eiq_angstrom": 1.1, "dist_to_f508_in_6msm_angstrom": 26.16, "dbsnp_ids": [ "rs397508621" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508621", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000266", "variant_label": "N1303H", "start_aa": 1303, "end_aa": 1303, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "24/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.7, "dist_to_f508_in_6msm_angstrom": 35.56, "dbsnp_ids": [ "rs121909042" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs121909042", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000267", "variant_label": "N1303K", "start_aa": 1303, "end_aa": 1303, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "24/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 11.62, "delta_ca_6msm_vs_8eiq_angstrom": 0.7, "dist_to_f508_in_6msm_angstrom": 35.56, "dbsnp_ids": [ "rs80034486" ], "pubmed_count": 7, "uniprot_description": "in CF; impaired maturation of glycan chains; has low in vitro channel activity at low temperature; dbSNP:rs80034486", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000268", "variant_label": "G1349D", "start_aa": 1349, "end_aa": 1349, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "25/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 14.14, "delta_ca_6msm_vs_8eiq_angstrom": 1.15, "dist_to_f508_in_6msm_angstrom": 29.06, "dbsnp_ids": [ "rs193922525" ], "pubmed_count": 2, "uniprot_description": "in CF; loss of bicarbonate transport; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity; dbSNP:rs193922525", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080325", "variant_label": "Q1352H", "start_aa": 1352, "end_aa": 1352, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "25/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 12.97, "delta_ca_6msm_vs_8eiq_angstrom": 1.19, "dist_to_f508_in_6msm_angstrom": 30.27, "dbsnp_ids": [ "rs113857788" ], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance; dbSNP:rs113857788", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000269", "variant_label": "A1364V", "start_aa": 1364, "end_aa": 1364, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "25/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.37, "delta_ca_6msm_vs_8eiq_angstrom": 0.83, "dist_to_f508_in_6msm_angstrom": 44.72, "dbsnp_ids": [ "rs397508670" ], "pubmed_count": 0, "uniprot_description": "in CBAVD; dbSNP:rs397508670", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_000270", "variant_label": "V1397E", "start_aa": 1397, "end_aa": 1397, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "26/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [ "6MSM", "5UAK", "8EIQ", "8EJ1" ], "delta_ca_6msm_vs_5uak_angstrom": 8.88, "delta_ca_6msm_vs_8eiq_angstrom": 1.04, "dist_to_f508_in_6msm_angstrom": 41.34, "dbsnp_ids": [ "rs397508691" ], "pubmed_count": 1, "uniprot_description": "in CF; dbSNP:rs397508691", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_048152", "variant_label": "R1453W", "start_aa": 1453, "end_aa": 1453, "span_type": "single_residue", "domain_id": "NBD2_C_terminal", "exon_label": "27/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [ "rs4148725" ], "pubmed_count": 0, "uniprot_description": "in dbSNP:rs4148725", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" }, { "uniprot_feature_id": "VAR_080326", "variant_label": "1473_1480del", "start_aa": 1473, "end_aa": 1480, "span_type": "multi_residue", "domain_id": "NBD2_C_terminal", "exon_label": "27/27", "near_splice_junction_le_3aa": false, "placed_in_pdb_entries": [], "delta_ca_6msm_vs_5uak_angstrom": "not stated", "delta_ca_6msm_vs_8eiq_angstrom": "not stated", "dist_to_f508_in_6msm_angstrom": "not stated", "dbsnp_ids": [], "pubmed_count": 1, "uniprot_description": "in CBAVD; uncertain significance", "source": "[UniProtKB:P13569 natural_variant + RCSB PDB 6MSM/5UAK/8EIQ/8EJ1]" } ] }, "footer": "Research tool, not medical advice. A database entry or structural domain annotation is not an interpretation of any person's genotype; that belongs with their clinical genetics team. Sources: ClinVar via NCBI E-utilities fixtures, MyVariant.info fixtures, UniProt P13569 (CC BY 4.0), RCSB PDB 5UAK, 6MSM, 8EIQ, 8EJ1 (CC0 1.0)." }