Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Genomics, |
RCV000236908 | SCV000256853 | pathogenic | Propionic acidemia | 2014-01-01 | criteria provided, single submitter | research | |
Invitae | RCV000236908 | SCV000631909 | pathogenic | Propionic acidemia | 2023-03-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg288 amino acid residue in PCCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20493181). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PCCA protein function. ClinVar contains an entry for this variant (Variation ID: 218262). This missense change has been observed in individual(s) with propionic acidemia (PMID: 27227689; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 288 of the PCCA protein (p.Arg288Lys). |