Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001269049 | SCV001448242 | likely pathogenic | Phenylketonuria | 2020-07-27 | reviewed by expert panel | curation | The NM_000277.1(PAH):c.935G>A (p.Gly312Asp) variant is a missense variant in exon 9/13 of PAH. It has been reported in at least 3 PKU cases in presumed trans with other Pathogenic variants (PM3; 1.5 points total), in two of whom BH4 deficiency was excluded (PP4_Moderate). It has been previously reported in presumed trans with the p.R241C variant (Pathogenic per ClinGen PAH VCEP) in two cases with mild PKU (plasma Phe 600–1200 μmol/L) and BH4 deficiency excluded (PMID: 30459323). It has also been reported in presumed trans with the p. R408W variant (Pathogenic by ClinGen PAH VCEP) in a patient with classic PKU and with undefined BH4 responsiveness. The variant is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). The variant is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.958) (PP3). Classification: Likely Pathogenic Supporting Criteria: PM2; PM3; PP4_Moderate; PP3 |
Baylor Genetics | RCV001269049 | SCV004209669 | likely pathogenic | Phenylketonuria | 2023-05-16 | criteria provided, single submitter | clinical testing | |
De |
RCV000089165 | SCV000119780 | not provided | not provided | no assertion provided | not provided |