Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806196 | SCV000946182 | likely pathogenic | Phenylketonuria | 2018-07-25 | criteria provided, single submitter | clinical testing | This variant has been observed in combination with another PAH variant in individuals affected with phenylketonuria (PMID: 28982351, Invitae). ClinVar contains an entry for this variant (Variation ID: 102753). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the His201 amino acid residue in PAH have been observed in affected individuals (PMID: 9521426, 20920871, 28982351). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 201 of the PAH protein (p.His201Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. |
De |
RCV000089002 | SCV000119606 | not provided | not provided | no assertion provided | not provided |