ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.478T>C (p.Tyr160His) (rs1555937197)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516785 SCV000613487 likely pathogenic not provided 2020-02-18 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Inconclusive segregation with disease. Variant is in an important domain.
Invitae RCV000544254 SCV000658913 pathogenic Charcot-Marie-Tooth Neuropathy X 2018-07-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 160 of the GJB1 protein (p.Tyr160His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease (CMT) in a single family (PMID: 19691535) and has also been reported in multiple individuals affected with CMT (PMID: 9361298, 18379723). ClinVar contains an entry for this variant (Variation ID: 447432). 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. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789189 SCV000928541 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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