Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000534214 | SCV000644156 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 332 of the MCCC2 protein (p.Arg332Gln). This variant is present in population databases (rs144203670, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 467811). 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%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001559390 | SCV001781606 | uncertain significance | not provided | 2019-08-20 | criteria provided, single submitter | clinical testing | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Natera, |
RCV001271401 | SCV001452527 | uncertain significance | Methylcrotonyl-CoA carboxylase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |