Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001093510 | SCV001250541 | likely pathogenic | Phenylketonuria | 2019-12-22 | reviewed by expert panel | curation | The c.1146C>G (p.Phe382Leu) variant in PAH has been reported in at least 1 individual with mild HPA (PP4; PMID: 18346471). The compound heterozygous individual also harbored the known pathogenic variant Arg252Trp (ClinVar 584) (PM3_suppporting). The c.1146C>G variant is absent in population databases (PM2). Computational prediction tools suggest that the variant may impact the protein (PP3). This variant generates the same amino acid change as c.1144T>C (p.Phe382Leu) which has been interpreted as Pathogenic by the ClinGen PAH Expert Panel (PS1). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PS1, PM2, PP4, PM3_supporting, PP3. |