ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5725A>G (p.Met1909Val) (rs750561317)

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 RCV000216841 SCV000276988 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000478945 SCV000567877 uncertain significance not provided 2016-12-29 criteria provided, single submitter clinical testing This variant is denoted ATM c.5725A>G at the cDNA level, p.Met1909Val (M1909V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Met1909Val 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 Met1909Val occurs at a position that is conserved in mammals and is not located in a known functional domain, In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Met1909Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000216841 SCV000913968 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-09 criteria provided, single submitter clinical testing
Invitae RCV000802222 SCV000942044 uncertain significance Ataxia-telangiectasia syndrome 2018-08-19 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1909 of the ATM protein (p.Met1909Val). 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 not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 232769). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.