Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003479002 | SCV004222622 | pathogenic | Phenylketonuria | 2023-12-30 | reviewed by expert panel | curation | The c.466G>C (p.Ala156Pro) variant in PAH has been reported in multiple individuals with PAH deficiency (BH4 deficiency excluded). (PMID: 26322415). This variant is absent in population databases. This variant was detected in trans with multiple pathogenic variants: p.H220P (PMID 26322415); c.611A>G (aka EX6-96A>G, PMID: 26600521); p.V5Sfs*33, p.R158W, p.R241C (2 patients), p.R261Q, p.R400T, p.T418P (PMID: 30050108). Functional studies show the PAH A156P mutant produces reduced protein (8.7% of wild type), with a residual enzyme activity of 10.4% (PMID 24327145). Computational evidence is conflicting. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM3_very-strong, PM2_supporting, PP4_Moderate, PS3_supporting. |
Mayo Clinic Laboratories, |
RCV000088936 | SCV005414120 | pathogenic | not provided | 2024-06-20 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM3_very_strong, PS3_supporting |
Juno Genomics, |
RCV003479002 | SCV005416849 | pathogenic | Phenylketonuria | criteria provided, single submitter | clinical testing | PM2_Supporting+PS3_Supporting+PM3_VeryStrong+PP4 | |
De |
RCV000088936 | SCV000119536 | not provided | not provided | no assertion provided | not provided |