ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1435_1441del (p.Arg479fs)

dbSNP: rs2136089949
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 RCV001873118 SCV002146606 pathogenic Multiple endocrine neoplasia, type 1 2022-05-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Lys559Glufs*38) have been determined to be pathogenic (PMID: 10090472; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation (PMID: 15331604, 16449969). While functional studies have not been performed to directly test the effect of this variant on MEN1 protein function, this suggests that disruption of this region of the protein is causative of disease. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg479Glyfs*78) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 132 amino acid(s) of the MEN1 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.