ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.116C>T (p.Ala39Val) (rs786204095)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168011 SCV000218662 pathogenic Charcot-Marie-Tooth Neuropathy X 2014-10-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 39 of the GJB1 protein (p.Ala39Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This sequence change has been reported in patients and families affected with CMT (PMID: 9888385, 12457340, 10400511, 10521546) and is not present in population databases. This sequence change causes mislocalization of the protein product in the cells. Functional studies showed that the wild type protein is targeted to the cell membrane whereas the mutant protein is localized to the endoplasmic reticulum and therefore interferes with the formation of gap junctions (PMID: 12111842). Because this sequence change is absent from the general population, has been observed in four independent CMT case reports, and disrupts the function of the GJB1 gene product, it has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789271 SCV000928624 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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