ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.415G>A (p.Val139Met) (rs104894812)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545060 SCV000658910 pathogenic Charcot-Marie-Tooth Neuropathy X 2020-06-22 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 139 of the GJB1 protein (p.Val139Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several families affected with Charcot-Marie-Tooth disease (PMID: 9272161, 7477983, 8266101, 9364054). ClinVar contains an entry for this variant (Variation ID: 10433). Experimental studies have shown that this missense change prevents the formation of functional gap junctions (PMID: 11325342, 8816997). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011178 SCV000031405 pathogenic Charcot-Marie-Tooth Neuropathy X Type 1 1995-10-01 no assertion criteria provided literature only
GeneReviews RCV000011178 SCV000040504 pathologic Charcot-Marie-Tooth Neuropathy X Type 1 2010-04-15 no assertion criteria provided curation Converted during submission to Pathogenic.
Inherited Neuropathy Consortium RCV000789810 SCV000929194 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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