ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.76G>A (p.Glu26Lys) (rs28931612)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000490040 SCV000576625 likely pathogenic not provided 2017-04-25 criteria provided, single submitter clinical testing The E26K variant in th eMEN1 gene has previously been published in association with multiple endocrine neoplasia type 1 (for examples, see Bartsch et al., 1998; Ellard et al., 2005; Schaaf et al., 2007; White et al., 2010). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E26K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, E26K is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.
Invitae RCV000817082 SCV000957622 uncertain significance Multiple endocrine neoplasia, type 1 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 26 of the MEN1 protein (p.Glu26Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in several individuals affected with multiple endocrine neoplasia type 1 (PMID: 9820618, 20231234, 12016472). This variant is also known as G186A (E26K) in the literature. ClinVar contains an entry for this variant (Variation ID: 16689). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
OMIM RCV000018169 SCV000038448 pathogenic Parathyroid adenoma, somatic 1997-08-01 no assertion criteria provided literature only

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.