ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2414G>A (p.Arg805Gln) (rs587782255)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130968 SCV000185883 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000466366 SCV000546780 uncertain significance Ataxia-telangiectasia syndrome 2019-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 805 of the ATM protein (p.Arg805Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs587782255, ExAC 0.02%). This variant has been reported in the literature in individuals with breast cancer (PMID: 17393301, 19781682). ClinVar contains an entry for this variant (Variation ID: 142128). 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.
GeneDx RCV000482755 SCV000564618 uncertain significance not provided 2018-12-03 criteria provided, single submitter clinical testing This variant is denoted ATM c.2414G>A at the cDNA level, p.Arg805Gln (R805Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant was observed in at least three patients with breast cancer and was absent in 2,399 control individuals from a large meta-analysis of ATM carriers (Broeks 2008, Tavtigian 2009, Tung 2015). ATM Arg805Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Arg805Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130968 SCV000903406 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-26 criteria provided, single submitter clinical testing

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.