ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.122T>C (p.Leu41Pro) (rs62642916)

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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 RCV001093507 SCV001250530 uncertain significance Phenylketonuria 2019-12-22 reviewed by expert panel curation The PAH variant c.122T>C (p.Leu41Pro) was found in one patient with mild PKU (serum phenylalanine levels between 600 and 1,200 micromol/liter) with the pathogenic variant c.728G>A (p.Arg243Gln) (CinVar ID: 591) (PMID: 10679941), and in a patient with moderate/mild PKU with the pathogenic variant c.838G>A (p.Glu280Lys) (CinVar ID: 580) (PMID: 22841515) PM3 (Points total = 1). This variant is absent in the gnomAD, ExAC, and PAGE population databases. In silico modeling predictions for this variant disagree. This variant is predicted to be tolerated by SIFT, possibly damaging by Polyphen 2-HVAR and disease-causing by Mutation Taster. In summary, this variant meets the criteria to be classified as uncertain significance (insufficient evidence for PAH). PAH-specific ACMG/AMP criteria applied: PM2, PM3, and PP4.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088809 SCV000119399 not provided not provided no assertion provided not provided

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