ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1372T>C (p.Tyr458His) (rs1064794762)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485418 SCV000569897 likely pathogenic not provided 2016-08-25 criteria provided, single submitter clinical testing A Y458H variant that is likely pathogenic has been identified in the PCDH19 gene. The Y458H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y458H variant 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, targeted parental test results indicate the Y458H variant is apparently de novo. Therefore, we now interpret Y458H as a likely pathogenic variant; however, the possibility that it is benign cannot be excluded.

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