ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.194A>G (p.Tyr65Cys)

dbSNP: rs104894819
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001245963 SCV001419290 pathogenic Charcot-Marie-Tooth Neuropathy X 2022-07-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr65 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 11562788), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GJB1 function (PMID: 15006706). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 10438). This missense change has been observed in individuals with X-linked Charcot-Marie-Tooth disease (PMID: 7477983, 27804109, 28469099; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 65 of the GJB1 protein (p.Tyr65Cys).
Athena Diagnostics RCV001659691 SCV001880842 pathogenic not provided 2021-06-08 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant shows a significant reduction in junctional conductance compared to the wild type (PMID: 15006706).
OMIM RCV000011183 SCV000031410 pathogenic Charcot-Marie-Tooth disease X-linked dominant 1 1995-10-01 no assertion criteria provided literature only

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