ClinVar Miner

Submissions for variant NM_001110219.3(GJB6):c.263C>T (p.Ala88Val) (rs28937872)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798432 SCV000938049 pathogenic Deafness, autosomal recessive 1A; Deafness, autosomal recessive 1b; Deafness, autosomal dominant 3b; Hidrotic ectodermal dysplasia syndrome 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 88 of the GJB6 protein (p.Ala88Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with disease in families affected with hidrotic ectodermal dysplasia (also known as Clouston syndrome) and has also been reported in additional unrelated affected individuals (PMID: 11017065, 27137747, 23863883, 14708603). ClinVar contains an entry for this variant (Variation ID: 5545). Experimental studies have shown that this missense change results in increased apoptosis, decreased gap junction conductance, and increased keratin expression, though data on the ability of the variant protein to localize to gap junctions conflict (PMID: 15213106, 24522190, 12419304, 24685692). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005883 SCV000026065 pathogenic Hidrotic ectodermal dysplasia syndrome 2000-10-01 no assertion criteria provided literature only

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