ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.416T>G (p.Val139Gly)

dbSNP: rs2147946105
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001948014 SCV002188084 pathogenic Charcot-Marie-Tooth Neuropathy X 2021-04-19 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 139 of the GJB1 protein (p.Val139Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val139 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9272161, 7477983, 8266101, 9364054). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (Invitae). In at least one individual the variant was observed to be de novo.

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