Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000436688 | SCV000517209 | pathogenic | not provided | 2015-05-13 | criteria provided, single submitter | clinical testing | The Q301K substitution has not been published as a pathogenic variant, nor has it beenreported as a benign polymorphism to our knowledge. Q301K was not observed in approximately 6500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. TheQ301K substitution occurs at a position that is conserved across species, in silico analysis predicts thisvariant is probably damaging to the protein structure/function, and missense variants at the same position(Q301P, Q301H) and in nearby residues (P292L/M, L293S, D296G, R297C/L/H, F299C, A300S/V,S303A/P, Q304R, I306V, G307D, L308F/V, A309D/V, S310Y/F, L311P) have been reported in theHuman Gene Mutation Database in association with phenylketonuria/ hyperphenylalaninemia (Stenson etal., 2014), supporting the functional importance of this region of the protein. Therefore, we interpretQ301K to be a pathogenic variant. |