Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002640732 | SCV003525832 | pathogenic | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2023-07-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 2203658). This missense change has been observed in individual(s) with 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 27033733; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 559 of the MCCC2 protein (p.Gly559Asp). |
| Gene |
RCV004719302 | SCV005325532 | likely pathogenic | not provided | 2023-09-12 | criteria provided, single submitter | clinical testing | Identified in the heterozygous state with a second MCCC2 variant in an infant identified by newborn screening, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Forsyth et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27033733) |