ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.394C>T (p.Arg132Ter) (rs121918241)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000001488 SCV000485871 pathogenic Methylmalonic acidemia with homocystinuria 2016-11-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153508 SCV000331092 pathogenic not provided 2015-10-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000001488 SCV000611284 pathogenic Methylmalonic acidemia with homocystinuria 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000153508 SCV000238989 pathogenic not provided 2018-11-26 criteria provided, single submitter clinical testing This variant is denoted c.394 C>T; p.Arg132Stop (R132X). R132X variant in the MMACHC gene has been reported previously in association with cblC deficiency (Lerner-Ellis, et al., 2006). The R132X variant accounts for approximately 8-20% of variants in the MMACHC gene, the range believed to reflect differences in population frequencies; it has been reported that many individuals with the R132X variant are of Middle Eastern origin (Lerner-Ellis et al., 2006, Lerner-Ellis et al., 2009). This variant is predicted to result in protein truncation.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000001488 SCV000746493 pathogenic Methylmalonic acidemia with homocystinuria 2017-12-03 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000001488 SCV000267132 pathogenic Methylmalonic acidemia with homocystinuria 2016-01-25 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000001488 SCV000699398 pathogenic Methylmalonic acidemia with homocystinuria 2017-04-06 criteria provided, single submitter clinical testing Variant summary: The MMACHC c.394C>T (p.Arg132X) variant results in a premature termination codon, predicted to cause a truncated or absent MMACHC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 12/120592 control chromosomes at a frequency of 0.0000995, which does not exceed the estimated maximal expected allele frequency of a pathogenic MMACHC variant (0.0030542). Multiple publications cite the variant in homozygous and compound heterozygous affected individuals and has been implicated to cause a late-onset affect. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000001488 SCV000640288 pathogenic Methylmalonic acidemia with homocystinuria 2018-11-14 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MMACHC gene (p.Arg132*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acids of the MMACHC protein. This variant is present in population databases (rs121918241, ExAC 0.07%). This variant has been reported as homozygous or in combination with another MMACHC variant in several individuals affected with methylmalonic acidemia and hyperhomocysteinemia of the cobalamin C (cblC) type (PMID: 16311595, 25511120, 26563984, 19760748 , 20631720, 24577983, 26149271) including the finding of the variant on the opposite chromosome (in trans) from a pathogenic variant. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 1423). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001488 SCV000021643 pathogenic Methylmalonic acidemia with homocystinuria 2009-07-01 no assertion criteria provided literature only
SingHealth Duke-NUS Institute of Precision Medicine RCV000721968 SCV000853111 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-06-07 no assertion criteria provided curation

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.