Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000106342 | SCV001370817 | uncertain significance | Phenylketonuria | 2020-04-10 | reviewed by expert panel | curation | The c.1171A>G (p.Ser391Gly) variant in PAH has been reported in at least 1 individual with classic PKU (PMID: 26666653). However, the patient genotype included pathogenic variants c.194 T>C; p.Ile65Thr (ClinVar: 636), c.1169A>G; p.Glu390Gly (ClinVar: 625), and this variant c.1171A>G (p.Ser391Gly) with phasing not confirmed. This variant was absent in population databases (PM2). Computational prediction tools suggest that the c.1171A>G variant may impact the protein (PP3). The alternate missense changes of Ser391Ile (interpreted as Pathogenic by the ClinGen PAH Expert Panel) and Ser391Thr (ClinVar 225136, Likely Pathogenic) have been reported at the same amino acid residue (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3. |
Inserm U 954, |
RCV000106342 | SCV000143841 | probable-pathogenic | Phenylketonuria | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |