Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000672941 | SCV005442776 | uncertain significance | Phenylketonuria | 2024-03-08 | reviewed by expert panel | curation | The c.587C>A (p.Ser196Tyr) variant in PAH has been reported in one individual with mild hyperphenylalanemia, without exclusion of BH4 deficiency (PMID: 23792259). In this individual, c.587C>A occurred de novo on the paternal allele, with confirmation of paternity. c.842+3G>C was present on the maternal allele (classified as likely pathogenic by PAH VCEP, Variation ID: 102871). In-vitro studies show 21% enzyme activity (PMID: 27620137). This variant is present below the 0.0002 allele frequency threshold for PAH in population databases. Multiple lines of computational evidence yield conflicting predictions regarding the effect of this variant (REVEL=0.542). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM3, PP4, PM2_supporting, PS3_supporting. |
Counsyl | RCV000672941 | SCV000798098 | uncertain significance | Phenylketonuria | 2018-02-28 | criteria provided, single submitter | clinical testing |