ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2818A>G (p.Lys940Glu) (rs1064795896)

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
Color RCV000771385 SCV000903711 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-26 criteria provided, single submitter clinical testing
GeneDx RCV000479895 SCV000572128 uncertain significance not provided 2017-12-11 criteria provided, single submitter clinical testing This variant is denoted ATM c.2818A>G at the cDNA level, p.Lys940Glu (K940E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAA>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Lys940Glu was not observed in large population cohorts (Lek 2016). Since Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Lys940Glu is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Lys940Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000549701 SCV000622364 uncertain significance Ataxia-telangiectasia syndrome 2018-05-24 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 940 of the ATM protein (p.Lys940Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 422618). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.