Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001093527 | SCV001250570 | uncertain significance | Phenylketonuria | 2019-11-05 | reviewed by expert panel | curation | This c.1066T>G (p.Y356D) variant in PAH was reported in 1 Southern Chinese patient with PAH deficiency (PMID: 26503515). DHPR activity, biopterin and/or pteridine analysis was performed to rule out other causes of hyperphenylalaninemia. This variant is present in African American populations at a frequency of 0.00003 and Native Hawaiian populations at a frequency of 0.00022 (PAGE). In silico modeling predicts that this missense variant is damaging (SIFT), probably damaging (PolyPhen2), and disease causing (mutation taster). In summary, this variant meets criteria to be classified as Uncertain Significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4, PP3. |