Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004823289 | SCV005442792 | pathogenic | Phenylketonuria | 2024-09-06 | reviewed by expert panel | curation | This c.548A>G (p.Glu183Gly) variant in PAH was reported in trans with pathogenic variants p.Arg111* and c.721C>T in 2 patients with PAH deficiency (>120 μmol/L Phe, BH4 deficiency excluded) (PMID: 28982351, 28754886). Residual enzyme activity was 9.1% for p.Glu183Gly compared to the wild-type PAH (PMID: 24327145). Computational evidence for this missense variant is predicted to be damaging (REVEL=0.977). This variant is absent from population databases gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM3_strong, PM2_supporting, PP4_moderate, PP3_strong, PS3_supporting. |