Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001375904 | SCV001572871 | pathogenic | Phenylketonuria | 2020-06-05 | reviewed by expert panel | curation | The p.Ex6_7_8del (c.510-735_912+434del) variant is a 4799bp deletion in PAH, a gene where loss of function is a known disease mechanism, and is predicted to lead to a frameshift at Gly171, premature protein truncation, and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD (structural variant version, gnomAD SVs v2.1) (PM2). It has been previously reported in one patient with PKU (BH4 deficiency excluded by sequencing of the genes in the BH4 cofactor metabolism pathway) (PP4_Moderate) (PMID: 23942198) in presumed trans with the p.F55L variant (Pathogenic per PAH VCEP) (0.5 points; PM3_Supporting). Classification: Pathogenic Supporting Criteria: PVS1; PM2; PP4_Moderate; PM3_Supporting |