Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001543652 | SCV001762329 | uncertain significance | Phenylketonuria | 2019-12-23 | reviewed by expert panel | curation | The c.1066T>C (p.Tyr356His variant in PAH has been not reported in a patient with PAH deficiency (to our knowledge). It was reported to the BioPKU database by Tyfield in 1996. This variant has an extremely low frequency in gnomAD (MAF=0.00016). There are conflicting interpretations of pathogenicity: SIFT (T); PolyPhen2 (P); MutationTaster (D); REVEL=0.794. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2. |
Labcorp Genetics |
RCV001543652 | SCV003293245 | pathogenic | Phenylketonuria | 2024-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 356 of the PAH protein (p.Tyr356His). This variant is present in population databases (rs62507320, gnomAD 0.02%). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 32668217; BIOPKU http://www.biopku.org). ClinVar contains an entry for this variant (Variation ID: 102512). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001543652 | SCV004201371 | pathogenic | Phenylketonuria | 2024-03-27 | criteria provided, single submitter | clinical testing | |
De |
RCV000088743 | SCV000119326 | not provided | not provided | no assertion provided | not provided |