ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1239_1240insGTCC (p.Cys414fs) (rs1114167524)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491151 SCV000579724 pathogenic Hereditary cancer-predisposing syndrome 2015-08-13 criteria provided, single submitter clinical testing
Invitae RCV000546948 SCV000628030 pathogenic Multiple endocrine neoplasia, type 1 2018-11-15 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEN1 gene (p.Cys409Valfs*41). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 202 amino acids of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MEN1-related disease. ClinVar contains an entry for this variant (Variation ID: 428066). Several different truncations located downstream of this variant (p.Arg516Profs*15, p.Arg516Glyfs*43,  p.Gln554*) have been determined to be pathogenic (PMID: 9215690,  11578300, 15635078, 17879353). This suggests that deletion of this region of the MEN1 protein is causative of disease. This frameshift 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.