Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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. |