Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000032132 | SCV004293506 | pathogenic | Propionic acidemia | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 112 of the PCCB protein (p.Gly112Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with propionic acidemia (PMID: 10910839, 29679984). ClinVar contains an entry for this variant (Variation ID: 38883). 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 PCCB protein function. Studies have shown that this missense change alters PCCB gene expression (PMID: 12757933). This variant disrupts the p.Gly112 amino acid residue in PCCB. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000032132 | SCV000055688 | not provided | Propionic acidemia | no assertion provided | literature only |