ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1438G>T (p.Gly480Cys) (rs79282516)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790782 SCV000225224 pathogenic not provided 2013-09-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004453 SCV001163498 likely pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000007607 SCV001167293 pathogenic Cystic fibrosis 2019-10-21 criteria provided, single submitter clinical testing This CFTR variant previously been identified in multiple individuals with a clinical presentation consistent with cystic fibrosis and is reported in ClinVar as pathogenic or likely pathogenic by two laboratories. Additionally, functional analysis support the deleterious effect of this missense change, located in the first nucleotide binding domain of the protein, on CFTR trafficking. This CFTR variant (rs79282516) is rare (<0.1%) in one large population dataset6 and absent from another (gnomAD: 1/31382 total alleles; 0.003187%; no homozygotes). We consider this variant to be pathogenic.
Myriad Women's Health, Inc. RCV000007607 SCV001193847 likely pathogenic Cystic fibrosis 2019-11-15 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.1438G>T(G480C) is classified as likely pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 11388756, 11823443, 1376016, 7757078 and 16132229. Classification of NM_000492.3(CFTR):c.1438G>T(G480C) is based on the following criteria: There is strong evidence of association with the variant and the relevant disease and there is functional data showing deficient protein function. Please note: this variant was assessed in the context of healthy population screening.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000007607 SCV001372434 likely pathogenic Cystic fibrosis 2020-06-14 criteria provided, single submitter clinical testing Variant summary: CFTR c.1438G>T (p.Gly480Cys) results in a non-conservative amino acid change located in the ABC transporter-like domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251304 control chromosomes. c.1438G>T has been reported in the literature in at-least one compound heterozygous individual affected with Pancreatically insufficient Cystic Fibrosis (example, Kristidis_1992). It has been subsequently cited among the CFTR gene mutations identified in the African American diaspora (example Stewart_2017, Castellani_2008) and is included in pan-ethnic carrier screening panels. At least one publication reports experimental evidence evaluating an impact on protein function (Smit_1995). The most pronounced variant effect results in defective intracellular processing, defective glycosylation and defective trafficking to the plasma membrane/protein mislocalization. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=1)/likely pathogenic(n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000007607 SCV001587475 pathogenic Cystic fibrosis 2020-08-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 480 of the CFTR protein (p.Gly480Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with cystic fibrosis (PMID: 7757078, 1376016, 9150159, 26708955). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 7187). This variant has been reported to affect CFTR protein function (PMID: 7757078, 27340661,11823443). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007607 SCV000027808 pathogenic Cystic fibrosis 1995-02-01 no assertion criteria provided literature only

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