Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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. |
De |
RCV000088874 | SCV000119471 | not provided | not provided | no assertion provided | not provided |