ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.828G>T (p.Met276Ile)

dbSNP: rs62514954
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001543637 SCV001762306 uncertain significance Phenylketonuria 2021-01-17 reviewed by expert panel curation The c.828G>T (p.Met276Ile) variant in PAH has been reported detected in a control clone from a subject who did not have PKU (PMID: 8364546, 9634518) This variant is absent from gnomAD, 1000G, ESP, and PAGE. Computational evidence is conflicting (Disease causing in MutationTaster, tolerated in SIFT, benign in PolyPhen2). There are 3 other missense changes at this amino acid: M276R (interpretation not provided in ClinVar, ID 102858); M276K (Likely Pathogenic in ClinVar, ID 102857); M276V (Likely Pathogenic in ClinVar, ID 102856). A different codon change leading to the same amino acid change, c.828G>A, has been interpreted as a variant of uncertain significance in ClinVar (ID 551519). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089120 SCV000119727 not provided not provided no assertion provided not provided

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