Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome- |
RCV001580733 | SCV001810489 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001580733 | SCV003450139 | likely pathogenic | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2023-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 439 of the MCCC1 protein (p.Val439Leu). This variant is present in population databases (rs398124352, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1210430). 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 MCCC1 protein function. This variant disrupts the p.Val439 amino acid residue in MCCC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22642865, 31901042; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |