ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.1A>T (p.Met1Leu) (rs386134250)

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 RCV000491567 SCV000579679 pathogenic Hereditary cancer-predisposing syndrome 2015-11-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
Invitae RCV000536890 SCV000628072 likely pathogenic Multiple endocrine neoplasia, type 1 2017-11-19 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the MEN1 mRNA. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Universal Mutation Database (PMID: 10612827) Two other different substitutions at this codon (c.1A>G and c.2T>A) have been reported in individuals affected with multiple endocrine neoplasia type I (MEN1) (PMID: 15714081, 26515642, Invitae database) and determined to be pathogenic. This suggests that the initiator methionine residue is critical for MEN1 protein function and that other missense substitutions at this position may also be pathogenic. 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.