Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000993643 | SCV001146775 | likely pathogenic | Phenylketonuria | 2019-08-02 | reviewed by expert panel | curation | The c.903G>T (p.Gln301His) variant in PAH has been reported in at least 1 individual with PKU however without indication of the genotype (BH4 deficiency ruled out) (PMID: 21307867) . The p.Gln301His variant is absent in gnomAD and the ESP population databases. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.831. This variant is located in the C-terminal aromatic amino acid hydroxylase domain and a different amino acid change at the same codon has been reported (PMID: 19292873 ). Overall, the c.903G>T variant is classified as likely pathogenic. PAH-specific ACMG/AMP criteria applied: PP3, PM2, PP4_M, PM5. |