ClinVar Miner

Submissions for variant NM_153212.3(GJB4):c.253A>C (p.Thr85Pro) (rs80358210)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413053 SCV000491251 pathogenic not provided 2016-11-08 criteria provided, single submitter clinical testing The T85P variant has been published previously in a large kindred where the variant was shown to co-segregate with disease in affected family members (Richard et al., 2003). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. T85P is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Although this substitution occurs at a position within the second transmembrane region where amino acids with similar properties to Threonine are tolerated across species, in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a missense variant in a nearby residue (C86S) has been reported in the Human Gene Mutation Database in association with erythrokeratodermia variabilis (Stenson et al., 2014), supporting the functional importance of this region of the protein.
OMIM RCV000005309 SCV000025487 pathogenic Erythrokeratodermia variabilis et progressiva 2 2003-04-01 no assertion criteria provided literature only

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