Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001966890 | SCV002254939 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-11-20 | 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 448 of the MCCC2 protein (p.Gly448Arg). This variant is present in population databases (rs766045910, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 33423264; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1471664). 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 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. |
| Revvity Omics, |
RCV001966890 | SCV003810819 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-01-24 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001966890 | SCV004194370 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-03-09 | criteria provided, single submitter | clinical testing |