ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.746C>T (p.Ala249Val)

gnomAD frequency: 0.00015  dbSNP: rs141676987
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248483 SCV001421971 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 249 of the MCCC2 protein (p.Ala249Val). This variant is present in population databases (rs141676987, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 972447). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV001248483 SCV002803886 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2022-05-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003433093 SCV004117460 uncertain significance MCCC2-related disorder 2023-01-10 criteria provided, single submitter clinical testing The MCCC2 c.746C>T variant is predicted to result in the amino acid substitution p.Ala249Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.048% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-70927955-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001248483 SCV002084909 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2020-03-25 no assertion criteria provided 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.