Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000012791 | SCV000631912 | pathogenic | Propionic acidemia | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 410 of the PCCB protein (p.Arg410Trp). This variant is present in population databases (rs121964959, gnomAD 0.006%). This missense change has been observed in individuals with propionic acidemia (PMID: 8411997, 12007220, 22033733). ClinVar contains an entry for this variant (Variation ID: 12011). 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: 12757933, 15890657, 15949719). For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000012791 | SCV000789286 | likely pathogenic | Propionic acidemia | 2017-01-17 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000012791 | SCV001136613 | pathogenic | Propionic acidemia | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000012791 | SCV001339066 | pathogenic | Propionic acidemia | 2020-03-13 | criteria provided, single submitter | clinical testing | Variant summary: PCCB c.1228C>T (p.Arg410Trp) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, C-terminal (IPR011763) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251032 control chromosomes (gnomAD). c.1228C>T has been reported in the literature in multiple individuals (both homozygous and compound heterozygous) affected with Propionic Acidemia (e.g. Chloupkova_2002, McCrory_2017, Kraus_2012, Gravel_1994). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant was found to have reduced enzymatic activity (Kraus_2012, Perez-Cedra_2003). Three ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic |
Baylor Genetics | RCV000012791 | SCV004205186 | pathogenic | Propionic acidemia | 2023-10-16 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000012791 | SCV000033031 | pathogenic | Propionic acidemia | 1999-01-01 | no assertion criteria provided | literature only | |
Gene |
RCV000012791 | SCV000055678 | not provided | Propionic acidemia | no assertion provided | literature only | ||
Natera, |
RCV000012791 | SCV002081489 | pathogenic | Propionic acidemia | 2021-01-15 | no assertion criteria provided | clinical testing |