ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.191G>A (p.Cys64Tyr) (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 2019-01-31 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 64 of the GJB1 protein (p.Cys64Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease and has been observed to segregate with disease in a family (PMID: 27862672, 27098783, 24768312, 25883816). 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"). 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: 11437164, 9187667), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789867 SCV000929252 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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