ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1523T>G (p.Phe508Cys) (rs74571530)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078978 SCV000110845 benign not specified 2016-04-14 criteria provided, single submitter clinical testing
Invitae RCV000007546 SCV000284996 benign Cystic fibrosis 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078978 SCV000304473 benign not specified criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000078978 SCV000538672 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Benign by Emory. Compund heterozygotes foe this variant and %508del variant were clinically normal, therefore this variant has been classified as benign by Kobayashi et al 1990. Frequency of the variant was higher in individuals with CBAVD (Havasi 2008). Phenotype does not meet reporting criteria.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078978 SCV000601049 likely benign not specified 2017-05-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000515132 SCV000608288 pathogenic Pancreatitis 2017-10-24 criteria provided, single submitter clinical testing The CFTR c.1523T>G; p.Phe508Cys variant has been published in the literature in individuals with monosymptomatic atypical cystic fibrosis (congenital bilateral absence of the vas deferens, pancreatitis) who also carried an additional pathogenic variant (Dork 1997, Havasi 2008, Ooi 2012). Additionally, our own internal data shows this variant is enriched in individuals with CFTR-related disease. However, this variant has also been published in asymptomatic individuals who also carried an additional pathogenic variant (Desgeorges 1994, Kobayashi 1990). The variant has been described in the dbSNP variant database (rs74571530) with an allele frequency of 0.1512 percent in European Americans in the Exome Variant Server and an allele frequency of 0.1609 in Europeans in the Exome Aggregation Consortium. The phenylalanine at codon 508 is well conserved across species and computational programs (PolyPhen2, SIFT) predict this variant is deleterious to protein function. Taken together, we predict this variant to be a very mild pathogenic variant that will not cause classic cystic fibrosis.
Johns Hopkins Genomics,Johns Hopkins University RCV000007546 SCV000886893 benign Cystic fibrosis 2019-10-30 criteria provided, single submitter clinical testing
CFTR-France RCV001009496 SCV001169591 pathogenic CFTR-related disorders 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001012006 SCV001172405 uncertain significance Inborn genetic diseases 2019-04-12 criteria provided, single submitter clinical testing Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV001009496 SCV001323779 uncertain significance CFTR-related disorders 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000007546 SCV000027747 benign Cystic fibrosis 1990-10-01 no assertion criteria provided literature only

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