ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1624T>G (p.Leu542Val) (rs587781366)

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 RCV000129168 SCV000183901 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
GeneDx RCV000211965 SCV000209688 uncertain significance not provided 2018-03-29 criteria provided, single submitter clinical testing This variant is denoted ATM c.1624T>G at the cDNA level, p.Leu542Val (L542V) at the protein level, and results in the change of a Leucine to a Valine (TTG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Leu542Val was not observed 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 Leu542Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000694975 SCV000823447 uncertain significance Ataxia-telangiectasia syndrome 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 542 of the ATM protein (p.Leu542Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine 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: 140912). 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. 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.