ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.586_608del (p.Ser196fs)

dbSNP: rs62895363
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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 RCV001269063 SCV001448285 pathogenic Phenylketonuria 2020-07-24 reviewed by expert panel curation The c.586_608del (p.Ser196fs) frameshift variant in PAH is predicted to undergo nonsense-mediated decay. This variant was reported in a Spanish patient with classic PKU in trans with pathogenic variant p.Arg261Gln. A defect in the synthesis or regeneration in the pathways of 6R-BH4 was ruled out by analyzing urinary pterin levels and by measuring the dihydropteridine reductase activity (PMID 27121329). This variant was also reported in another Spanish patient with moderate PKU and identified with the pathogenic variant p.I65T (PMID 15464430). This variant is absent from gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, and PP4 moderate.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088992 SCV000119596 not provided not provided no assertion provided not provided

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