ClinVar Miner

Submissions for variant NM_172250.3(MMAA):c.742C>T (p.Gln248Ter) (rs757548934)

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
Integrated Genetics/Laboratory Corporation of America RCV000586897 SCV000699977 pathogenic Methylmalonic acidemia 2016-12-30 criteria provided, single submitter clinical testing Variant summary: The MMAA c.742C>T (p.Gln248X) variant results in a premature termination codon, predicted to cause a truncated or absent MMAA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The truncated protein is expected to remove the 170 amino acids in the C-terminus, which includes part of the P-loop containing nucleoside triphosphate hydrolase domain. One in silico tool predicts a damaging outcome for this variant. Xiong_2015 predicted a large splicing change induced by this variant. However, this change was not predicted by 5/5 splice prediction tools. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/121506 control chromosomes at a frequency of 0.0000329 (all alleles are from East Asian subpopuation), which does not exceed the estimated maximal expected allele frequency of a pathogenic MMAA variant (0.0018257). This variant has been reported in at least two patients. Taken together, this variant is classified as pathogenic.

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.