ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.494G>A (p.Cys165Tyr)

dbSNP: rs1057521111
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
GeneDx RCV000442726 SCV000521097 likely pathogenic not provided 2022-10-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with a personal and/or family history consistent with pathogenic variants in this gene (Damjanovic et al., 2020; Yavropoulou et al., 2022); This variant is associated with the following publications: (PMID: 17879353, 24756045, 17853334, 12112656, 15670192, 30820182, 9989505, 35407574, 32901291)
Labcorp Genetics (formerly Invitae), Labcorp RCV000632126 SCV000753230 likely pathogenic Multiple endocrine neoplasia, type 1 2022-12-07 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 165 of the MEN1 protein (p.Cys165Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (MEN1) (PMID: 15670192, 30820182). ClinVar contains an entry for this variant (Variation ID: 381624). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. This variant disrupts the p.Cys165 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12112656, 17853334, 24756045). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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.