ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.191G>A (p.Cys64Tyr)

dbSNP: rs1602348897
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001065214 SCV001230164 pathogenic Charcot-Marie-Tooth Neuropathy X 2022-08-21 criteria provided, single submitter clinical testing This variant disrupts the p.Cys64 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 9187667, 11437164), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. 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: 637608). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 24768312, 25883816, 27098783, 27862672). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 64 of the GJB1 protein (p.Cys64Tyr).
Inherited Neuropathy Consortium RCV000789867 SCV000929252 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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