ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6178C>T (p.Arg2060Cys) (rs587778078)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115227 SCV000214922 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000115227 SCV000687676 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-11 criteria provided, single submitter clinical testing
GeneDx RCV000766513 SCV000149136 uncertain significance not provided 2018-08-03 criteria provided, single submitter clinical testing This variant is denoted ATM c.6178C>T at the cDNA level, p.Arg2060Cys (R2060C) at the protein level, and results in the change of an Arginine to a Cysteine (CGC>TGC). This variant was observed in 1/331 healthy individuals of European ancestry undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. This variant was also absent among 13,087 breast cancer cases but present in 1/5488 control individuals in a breast cancer case-control study (Decker 2017). ATM Arg2060Cys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the FAT domain (Stracker 2013). 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 Arg2060Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
ITMI RCV000120152 SCV000084293 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000204186 SCV000259404 uncertain significance Ataxia-telangiectasia syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2060 of the ATM protein (p.Arg2060Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs587778078, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127422). 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.