ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8506A>G (p.Met2836Val) (rs879253968)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235391 SCV000292992 uncertain significance not provided 2016-02-09 criteria provided, single submitter clinical testing This variant is denoted ATM c.8506A>G at the cDNA level, p.Met2836Val (M2836V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant was observed in at least one individual with Ataxia Telangiectasia (A-T) who also carried a nonsense variant in ATM, though phase was not determined (Exley 2011, Carney 2012). Although ATM Met2836Val has been reported by one group to result in reduced ATM protein expression and no ATM kinase activity, it has not, to our knowledge, been published in additional A-T patients nor has it been published in regards to cancer risk in heterozygous carriers (Exley 2011, Carney 2012). ATM Met2836Val 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 Methionine and Valine share similar properties, this is considered a conservative amino acid substitution. ATM Met2836Val occurs at a position that is conserved across species and is located in the within PI3K/PI4K kinase domain (Tavtigian 2009). 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 Met2836Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000814842 SCV000955271 uncertain significance Ataxia-telangiectasia syndrome 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 2836 of the ATM protein (p.Met2836Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with ataxia telangiectasia (PMID: 21459046). ClinVar contains an entry for this variant (Variation ID: 245835). Experimental studies have shown that this missense change impairs the kinase activity of the ATM protein (PMID: 21459046). 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.