Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000674910 | SCV002032230 | likely pathogenic | Phenylketonuria | 2021-12-12 | reviewed by expert panel | curation | The c.870T>G (p.His290Gln) variant in PAH has been reported in one patient with classic PKU (BH4 deficiency not excluded; PP4; PMID: 26210745). It was detected with known pathogenic variant p.R261Q, but parental testing was not reported/performed. Functional studies show low but measurable activities for tyrosine formation and greatly decreased the affinity for iron (PMID: 18477464). This variant is absent from 1000G, ESP, ExAC and gnomAD. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.924. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3, PM3_supporting, PS3_supporting. |
Counsyl | RCV000674910 | SCV000800322 | uncertain significance | Phenylketonuria | 2018-05-31 | criteria provided, single submitter | clinical testing |