ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.548T>C (p.Val183Ala)

gnomAD frequency: 0.00001  dbSNP: rs780926592
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706068 SCV000835099 uncertain significance Cobalamin C disease 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 183 of the MMACHC protein (p.Val183Ala). This variant is present in population databases (rs780926592, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MMACHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 582087). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MMACHC protein function. 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.
GeneDx RCV002221579 SCV002498910 uncertain significance not provided 2022-04-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV000706068 SCV002815808 uncertain significance Cobalamin C disease 2022-03-12 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000706068 SCV004178194 uncertain significance Cobalamin C disease 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001277245 SCV001464152 uncertain significance Methylmalonic acidemia with homocystinuria cblC 2020-01-17 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.