ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.277C>T (p.Arg93Cys)

gnomAD frequency: 0.00006  dbSNP: rs746274670
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
Counsyl RCV000669202 SCV000793931 uncertain significance Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-09-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001815368 SCV002062680 likely pathogenic not provided 2021-11-01 criteria provided, single submitter clinical testing
Invitae RCV001815368 SCV003439439 likely pathogenic not provided 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 93 of the MUT protein (p.Arg93Cys). This variant is present in population databases (rs746274670, gnomAD 0.007%). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 26270765, 36717752). ClinVar contains an entry for this variant (Variation ID: 553695). 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 MUT protein function with a positive predictive value of 95%. This variant disrupts the p.Arg93 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1670635, 16281286, 16490061). 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.
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, RCV000669202 SCV001245436 uncertain significance Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 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.