ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.34G>A (p.Gly12Ser) (rs1555936999)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552022 SCV000658908 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2017-07-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 12 of the GJB1 protein (p.Gly12Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family affected with Charcot-Marie-Tooth disease, type X (PMID: 8266101). Experimental studies have shown that this missense change alters the structure of the GJB1 (also known as Cx32) protein such that a functional channel is not formed and the mutant protein is mislocalized to the Golgi apparatus instead of the plasma membrane (PMID: 9354338, 11325342, 15006706, 19638273, 9364054, 10646523, 22705201). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Inherited Neuropathy Consortium RCV000789811 SCV000929195 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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