ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1208A>G (p.Asn403Ser)

gnomAD frequency: 0.00016  dbSNP: rs142887940
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002003162 SCV002274670 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-07-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 403 of the MCCC2 protein (p.Asn403Ser). This variant is present in population databases (rs142887940, gnomAD 0.02%). This missense change has been observed in individual(s) with 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. ClinVar contains an entry for this variant (Variation ID: 1483421). 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%. This variant disrupts the p.Asn403 amino acid residue in MCCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16835865). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003227056 SCV003923570 likely pathogenic not provided 2025-01-06 criteria provided, single submitter clinical testing Observed in the heterozygous state in one individual from a cohort of patients with mitochondrial complex I deficiency (PMID: 20818383); 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: 25087612, 20818383, 16835865)
Fulgent Genetics, Fulgent Genetics RCV002003162 SCV005666619 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-05-07 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.