ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.737C>A (p.Ala246Asp) (rs199475610)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000089067 SCV000516538 pathogenic not provided 2015-03-26 criteria provided, single submitter clinical testing The A246D missense variants in the PAH gene has been reported as a pathogenicvariant in the PAH Consortium database. The A246D substitution was reported in a patient withphenylketonuria (PKU) from Western Scotland (Tyfield et al., 1997). To our knowledge, information onthe phenotype of patients harboring the A246D variant has not been published. A246D is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residuesdiffer in polarity, charge, size and/or other properties, and a missense variant at the same position(A246V) and in many nearby residues (R243L/Q, P244L, V245L/E/A, G247S/R/V/D, L248R/P,L249F/P/H) have been reported in the Human Gene Mutation Database in association with PKU (Stensonet al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpretA246D to be a pathogenic variant.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089067 SCV000119673 not provided not provided no assertion provided not provided

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