ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.554A>T (p.Asp185Val) (rs1064794683)

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 RCV000487365 SCV000569717 uncertain significance not provided 2016-03-24 criteria provided, single submitter clinical testing This variant is denoted MEN1 c.539A>T at the cDNA level, p.Asp180Val (D180V) at the protein level, and results in the change of an Aspartic Acid to a Valine (GAT>GTT). This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or benign polymorphism. However, it has been reported as a somatic variant in a sporadic parathyroid adenoma (Pardi 2013). MEN1 Asp180Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MEN1 Asp180Val occurs at a position that is conserved across species and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MEN1 Asp180Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001049493 SCV001213543 uncertain significance Multiple endocrine neoplasia, type 1 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 180 of the MEN1 protein (p.Asp180Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 420754). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.