ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.208T>C (p.Ser70Pro)

dbSNP: rs63048261
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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 RCV002259586 SCV002540153 likely pathogenic Phenylketonuria 2022-03-11 reviewed by expert panel curation The c.208T>C (p.Ser70Pro) variant in PAH has been reported in at least four individuals with hyperphenylalanemia, including at least one for whom BH4 deficiency was excluded (PMID: 9860305, PMID: 21307867). Of these, two were siblings who also had p.Arg241His (PMID: 22330942), which is classified as pathogenic by PAH VCEP (Variation ID: 102804), without documentation of parental testing to establish phase. In-vitro studies show 20% enzyme activity (PMID: 9860305). This variant is absent from population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP3, PP4, PM2, PM3_Supporting, PS3_supporting.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088874 SCV000119471 not provided not provided no assertion provided not provided

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