Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001269081 | SCV001448307 | pathogenic | Phenylketonuria | 2020-10-15 | reviewed by expert panel | curation | This c.804C>A (p.Tyr268Ter) variant in PAH was observed in a patient with classical PKU detected with pathogenic variant p.Arg243Gln (PMID: 28982351). This variant is absent from controls in population databases. This is a nonsense variant in exon 7 out of 13 coding exons. The variant is predicted to undergo nonsense mediated mRNA decay (NMD). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM3, PM2, and PP4. |
Neuberg Centre For Genomic Medicine, |
RCV001269081 | SCV002073218 | pathogenic | Phenylketonuria | criteria provided, single submitter | clinical testing | The stop gained p.Y268* in PAH (NM_000277.3) has been classified as Pathogenic by the ClinGen expert curation panel. The p.Y268* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function. For these reasons, this variant has been classified as Pathogenic. |