ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.926C>A (p.Ala309Asp) (rs62642935)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668228 SCV000792796 likely pathogenic Phenylketonuria 2017-07-14 criteria provided, single submitter clinical testing
Invitae RCV000668228 SCV001395501 pathogenic Phenylketonuria 2019-10-04 criteria provided, single submitter clinical testing This sequence change replaces alanine with asparagine at codon 309 of the PAH protein (p.Ala309Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another PAH variant in several individuals affected with PKU (PMID: 7913581, 16256386, 23430918, Invitae). ClinVar contains an entry for this variant (Variation ID: 102897). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C65"). This variant disrupts the p.Ala309 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12655546, 21871829, 26666653, 27121329, 15459954, 16504182, 12655546). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089160 SCV000119774 not provided not provided no assertion provided not provided

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