Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001093509 | SCV001250540 | likely pathogenic | Phenylketonuria | 2019-12-22 | reviewed by expert panel | curation | The PAH variant c.460T>C (p.Tyr154His) has been reported in three Chinese individuals with PHA deficiency (Phe levels >120 microM). The PAH variant c.460T>C (p.Tyr154His) was found in trans with the PAH pathogenic variant c.331C>T (p.Arg111Ter)(ClinVar ID: 581) in a Chinese patient with classical PKU (Phe levels >20 mg/dl). All mutations identified were confirmed by analyzing parental DNA. BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PMID: 26322415). The PAH variant c.460T>C (p.Tyr154His) was found as a homozygous occurrence in a Chinese patient with classical PKU (Phe greater than or equal to 1200 micromol/L) (PM3 Points= 1*0.5=0.5) (PMID:16256386). This variant was also reported in two other Chinese patients with undetermined PKU/MHP phenotype (PMID: 26503515, and PMID: 19915519). The PAH variant c.460T>C (p.Tyr154His) is absent from the gnomAD, ExAC, 1000 Genomes, and ESP population databases. In silico modeling, predictions support that this missense variant could have a deleterious effect on the PAH gene or gene product. This variant is predicted to be deleterious by SIFT, probably damaging by PolyPhen2- HumVar, and disease-causing by Mutation Taster. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP3, and PP4_Moderate. |
| Baylor Genetics | RCV001093509 | SCV004209697 | pathogenic | Phenylketonuria | 2023-02-28 | criteria provided, single submitter | clinical testing | |
| De |
RCV000088933 | SCV000119533 | not provided | not provided | no assertion provided | not provided |