ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1028A>G (p.Tyr343Cys) (rs62507265)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000088708 SCV000582433 likely pathogenic not provided 2015-10-01 criteria provided, single submitter clinical testing The Y343C variant was not observed in approximately 6500 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 Y343C 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. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same residue (Y343D and Y343F) and in nearby residues (D388Y, I340T, K341/R/T, A342T/P, G344R/S/D/V, A345S/T, G346R/E, L347F, L348V) have been reported in the Human Gene Mutation Database in association with phenylketonuria (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret the Y343C variant to be likely pathogenic; however, the possibility that it is benign cannot be excluded.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088708 SCV000119288 not provided not provided no assertion provided not provided

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