ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.589G>A (p.Gly197Arg) (rs764080545)

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
Ambry Genetics RCV000217038 SCV000274532 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-15 criteria provided, single submitter clinical testing Insufficient or inconclusive evidence
GeneDx RCV000235397 SCV000293593 uncertain significance not provided 2015-11-24 criteria provided, single submitter clinical testing This variant is denoted ATM c.589G>A at the cDNA level, p.Gly197Arg (G197R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Gly197Arg 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 Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Gly197Arg occurs at a position that is conserved across species and is not located in a known functional domain (Tavtigian 2009, Stracker 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether ATM Gly197Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001069719 SCV001234909 uncertain significance Ataxia-telangiectasia syndrome 2019-02-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 197 of the ATM protein (p.Gly197Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs764080545, ExAC 0.002%). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 230853). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.