ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.100A>G (p.Met34Val) (rs1569215061)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684965 SCV000812430 pathogenic Charcot-Marie-Tooth Neuropathy X 2018-04-13 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 34 of the GJB1 protein (p.Met34Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with X-linked Charcot-Marie-Tooth disease and to segregate with X-linked Charcot-Marie-Tooth disease in a family (PMID: 9018031, 11571214). Experimental studies have shown that this missense change results in abnormal protein cellular localization (PMID: 12460545). Different missense substitutions at this codon (p.Met34Ile, p.Met34Thr) have been determined to be pathogenic (PMID: 8829637, 9361298, 12460545). This suggests that the methionine residue is critical for GJB1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001172018 SCV001334947 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789244 SCV000928596 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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