ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1415_1428del (p.Ala472fs)

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
Invitae RCV000813744 SCV000954115 pathogenic Multiple endocrine neoplasia, type 1 2018-11-20 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Ala467Glyfs*59). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 144 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with multiple endocrine neoplasia type 1 (MEN1) (PMID: 17853334). This variant is also known as 1509del14 in the literature. This variant deletes the functionally conserved NLS2 domain of the MEN1 protein. Experimental studies have shown that disruption of this region abrogates the ability of MEN1 to bind DNA, regulate target gene expression, and inhibit cell proliferation (PMID: 15331604, 16449969). This variant disrupts the C-terminus of the MEN1 protein. Other variant(s) that disrupt this region (p.Gln554*) have been determined to be pathogenic (PMID: 11578300, 17853334, 17158764). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been 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.