ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1194_1195TG[1] (p.Val399fs) (rs1227030642)

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
Invitae RCV000701062 SCV000829844 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2019-09-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val399Glufs*24) in the MUT gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous in an individual affected with methylmalonic acidemia (PMID: 16281286). Loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000701062 SCV001137133 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2019-05-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001174604 SCV001337798 pathogenic Methylmalonic acidemia 2020-01-21 criteria provided, single submitter clinical testing Variant summary: MUT c.1196_1197delTG (p.Val399GlufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251324 control chromosomes (gnomAD). c.1196_1197delTG has been reported in the literature in one homozygous individual affected with Methylmalonic Acidemia (Worgan_2006). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001271708 SCV001453056 pathogenic Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency 2020-09-16 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.