Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000012795 | SCV000793689 | likely pathogenic | Propionic acidemia | 2017-08-22 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000012795 | SCV001136606 | pathogenic | Propionic acidemia | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000012795 | SCV001591310 | pathogenic | Propionic acidemia | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 168 of the PCCB protein (p.Glu168Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with propionic acidemia (PMID: 9683601, 20549364). ClinVar contains an entry for this variant (Variation ID: 12015). 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 PCCB protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PCCB function (PMID: 11749052, 12757933). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000012795 | SCV002074157 | pathogenic | Propionic acidemia | 2022-01-02 | criteria provided, single submitter | clinical testing | Variant summary: PCCB c.502G>A (p.Glu168Lys) results in a conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, N-terminal domain (IPR011762) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-06 in 166868 control chromosomes. c.502G>A has been reported in the literature as homozygous and compound heterozygous genotypes in multiple individuals affected with Propionic Acidemia (example, Rodriguez-Pombo_1998). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (example, Perez-Cedra_2003). The most pronounced variant effect results in undetectable levels (approximately 1%) of normal propionyl-CoA carboxylase (PCC) enzyme activity in vitro. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV000012795 | SCV002811590 | pathogenic | Propionic acidemia | 2021-11-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000012795 | SCV004205188 | pathogenic | Propionic acidemia | 2023-10-10 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000012795 | SCV000033035 | pathogenic | Propionic acidemia | 1998-08-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000012795 | SCV000055690 | not provided | Propionic acidemia | no assertion provided | literature only | ||
| Natera, |
RCV000012795 | SCV002081475 | pathogenic | Propionic acidemia | 2021-03-04 | no assertion criteria provided | clinical testing |