ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.175G>C (p.Gly59Arg) (rs104894410)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588875 SCV000698232 pathogenic Palmoplantar keratoderma-deafness syndrome 2017-07-11 criteria provided, single submitter clinical testing Variant summary: The GJB2 c.175G>C (p.Gly59Arg) variant involves the alteration of a conserved nucleotide and is located in N-terminal region of the protein (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (PP3). This variant is absent in 121328 control chromosomes from ExAC (PM2). This variant has been reported in at least one patient with autosomal dominant palmoplanter keratoderma with deafness (Leonard_2005), and this variant as a confirmed de novo mutation with confirmed parentage (PS2). Other missense variants at this residue (namely p.Gly59Asp, p.Gly59Ala and p.Gly59Ser) have also been reported in association with autosomal dominant form of hearing loss with variable phenotypic expressivity (PM1, PM5). Multiple databases concluded its pathogenicity as pathogenic (PP5). Taken together, according to ACMG guideline, this variant is classified as pathogenic.

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