ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.648dup (p.Glu217fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002811327 SCV003204102 pathogenic Cobalamin C disease 2022-06-08 criteria provided, single submitter clinical testing This variant is present in population databases (rs773968018, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MMACHC-related conditions. This variant disrupts a region of the MMACHC protein in which other variant(s) (p.Tyr222*) have been determined to be pathogenic (PMID: 16311595, 19767224, 30157807). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu217Argfs*28) in the MMACHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the MMACHC protein.

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.