ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1427G>A (p.Trp476Ter) (rs1060499991)

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 RCV000474300 SCV000541228 pathogenic Multiple endocrine neoplasia, type 1 2017-09-02 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the MEN1 mRNA at codon 471 (p.Trp471*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with multiple endocrine neoplasia 1 (MEN1) (PMID: 22026581). A different variant c.1413G>A giving rise to the same protein effect observed here (p.Trp471*) has been reported in a patient as well as a in a large family affected with MEN1-related disease (PMID: 10090472, 10435055). This nonsense change truncates 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) 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.