Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Natera, |
RCV000414788 | SCV007530769 | likely pathogenic | Propionic acidemia | 2024-10-29 | criteria provided, single submitter | clinical testing | The c.425G>A variant in PCCA is a missense variant predicted to cause substitution of glycine to aspartic acid at amino acid 142. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 27959697, 22156789, 31392117). This variant has been identified in one or more affected individual with a phenotype highly consistent with the associated gene (PMID: 27959697, 22156789, 31392117). Functional studies show that this variant may disrupt protein function (PMID: 36211601). Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Likely Pathogenic. |
| Genomic Medicine Center of Excellence, |
RCV003984829 | SCV004801163 | pathogenic | Pontocerebellar hypoplasia type 2D | 2024-03-14 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV000414788 | SCV001401517 | pathogenic | Propionic acidemia | 2025-10-28 | 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 142 of the PCCA protein (p.Gly142Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with propionic acidemia (PMID: 22156789, 30705822). ClinVar contains an entry for this variant (Variation ID: 203880). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PCCA protein function with a positive predictive value of 95%. This variant disrupts the p.Gly142 amino acid residue in PCCA. Other variant(s) that disrupt this residue have been observed in individuals with PCCA-related conditions (PMID: 30274917), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Pathology and Clinical Laboratory Medicine, |
RCV000414788 | SCV000996285 | pathogenic | Propionic acidemia | criteria provided, single submitter | clinical testing | Compatible metabolite assay | |
| Baylor Genetics | RCV000414788 | SCV000328820 | pathogenic | Propionic acidemia | 2024-03-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000186085 | SCV000239109 | pathogenic | not provided | 2019-09-16 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 30014764, 22156789, 27959697, 30274917, 27629047, 30705822, 33101984) |
| Clinical Laboratory Sciences Program |
RCV000414788 | SCV003927937 | pathogenic | Propionic acidemia | 2023-04-01 | no assertion criteria provided | clinical testing | |
| Biochemical Molecular Genetic Laboratory, |
RCV000414788 | SCV001133014 | pathogenic | Propionic acidemia | 2019-09-26 | no assertion criteria provided | clinical testing |