Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003498338 | SCV004310637 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 352 of the MCCC2 protein (p.Gly352Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Gly352 amino acid residue in MCCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16010683, 19706617, 25356967). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |