Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000993624 | SCV001146752 | pathogenic | Phenylketonuria | 2019-04-04 | reviewed by expert panel | curation | The c.904delT (p.Ser303Profs*38) variant in PAH has been observed in at least one patient with classic PKU (plasma phenylalanine greater than 1200 micromolar) with a known pathogenic variant p.Ser70del (PMID:16256386). This variant is absent in population databases including: 1000 Genomes, ESP, and extremely low in gnomAD. This is a single base pair deletion that creates a frameshift in exon 9 and is predicted to undergo nonsense mediated decay with the truncated region critical to protein function. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4. |
Labcorp Genetics |
RCV000993624 | SCV003441154 | pathogenic | Phenylketonuria | 2024-05-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser303Profs*38) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with PAH-related conditions (PMID: 26503515, 29316886). ClinVar contains an entry for this variant (Variation ID: 102888). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000993624 | SCV005053842 | pathogenic | Phenylketonuria | 2023-12-21 | criteria provided, single submitter | clinical testing | |
Juno Genomics, |
RCV000993624 | SCV005416484 | pathogenic | Phenylketonuria | criteria provided, single submitter | clinical testing | PVS1+PM2_Supporting+PM3 | |
De |
RCV000089150 | SCV000119763 | not provided | not provided | no assertion provided | not provided |