Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001389298 | SCV001590609 | pathogenic | Phenylketonuria | 2020-07-30 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PAH protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu76 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12655546, 24401910, 11935335). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in individual(s) with PAH-related conditions (PMID: 8632937, Invitae). ClinVar contains an entry for this variant (Variation ID: 102634). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with alanine at codon 76 of the PAH protein (p.Glu76Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
De |
RCV000088877 | SCV000119474 | not provided | not provided | no assertion provided | not provided |