Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001093506 | SCV001250529 | likely pathogenic | Phenylketonuria | 2024-09-06 | reviewed by expert panel | curation | The c.442G>C (p.Gly148Arg) variant in PAH is a missense variant that is predicted damaging by REVEL (REVEL score 0.947) (PP3_Strong). It is absent from gnomAD v2.1.1 (PM2_Supporting). It has been reported in at least 1 Chinese patient with PAH deficiency with BH4 deficiency excluded (PMID: 26503515, 30050108) (PP4_Moderate), and has been reported in unknown phase with the pathogenic variant p.Arg243Gln (ClinVar ID: 591) (PM3_Supporting). Multiple different missense variants at the same site have been reported likely pathogenic in ClinVar, including c.443G>A (p.Gly148Asp) (ClinVar ID: 872837), c.443G>T (p.Gly148Val) (ClinVar ID: 552657), c.442G>A (p.Gly148Ser) (ClinVar ID: 102680) (PM5_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: PM2_Supporting, PM5_Supporting, PP4_Moderate, PP3_Strong. |