Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001376966 | SCV001574175 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 517 of the MCCC2 protein (p.Gly517Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 21071250; internal data). ClinVar contains an entry for this variant (Variation ID: 1066068). 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 MCCC2 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987854 | SCV004803720 | uncertain significance | not specified | 2024-01-23 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.1549G>A (p.Gly517Arg) results in a non-conservative amino acid change located in the acetyl-coenzyme A carboxyltransferase, C-terminal domain (IPR011763) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251394 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1549G>A has been reported in the literature as a compound heterozygous genotype in an individual affected with Methylcrotonyl-CoA Carboxylase Deficiency (Nguyen_2011). These data do not allow any strong conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 21071250). ClinVar contains an entry for this variant (Variation ID: 1066068). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV001376966 | SCV005666625 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-05-02 | criteria provided, single submitter | clinical testing |