Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001857428 | SCV004222623 | pathogenic | Phenylketonuria | 2023-10-15 | reviewed by expert panel | curation | The c.1127del (p.Asn376fs) variant in PAH is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 11/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). It was reported in a Mexican patient with classic PKU with the pathogenic variant c.1066-11G>A (PMID: 24941924; PP4, PM3_supporting). This variant has an extremely low frequency in gnomAD (MAF=0.00002895). In summary, this variant meets the criteria to be classified as pathogenic for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PVS1, PM2_supporting, PM3_supporting, PP4. |
Invitae | RCV001857428 | SCV002243444 | pathogenic | Phenylketonuria | 2023-04-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn376Ilefs*24) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). This variant is present in population databases (rs62642921, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 102532). This premature translational stop signal has been observed in individual(s) with phenylketonuria (PMID: 24941924). |
Baylor Genetics | RCV001857428 | SCV004209702 | pathogenic | Phenylketonuria | 2023-02-15 | criteria provided, single submitter | clinical testing | |
De |
RCV000088765 | SCV000119349 | not provided | not provided | no assertion provided | not provided |