Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002260490 | SCV002540131 | pathogenic | Phenylketonuria | 2020-12-08 | reviewed by expert panel | curation | The NM_000277.3(PAH):c.703C>T (p.Gln235Ter) nonsense variant occurs in exon 6 of 13 and is predicted to result in NMD. It has been reported in one classic PKU patient (http://www.fedoa.unina.it/9088/1/TESI%20DOTTORATO%20ALESSIA%20PALMIERI.pdf) and is found at an extremely low allele frequency in gnomAD (MAF of 0.00006152 in the African/African-American population). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4. |
Labcorp Genetics |
RCV002260490 | SCV003441286 | pathogenic | Phenylketonuria | 2023-09-06 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia (PMID: 23352163). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln235*) 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). ClinVar contains an entry for this variant (Variation ID: 1693231). For these reasons, this variant has been classified as Pathogenic. |