ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3299C>T (p.Thr1100Met) (rs189445371)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215728 SCV000273043 likely benign Hereditary cancer-predisposing syndrome 2017-08-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Color RCV000215728 SCV000911595 likely benign Hereditary cancer-predisposing syndrome 2017-05-02 criteria provided, single submitter clinical testing
GeneDx RCV000159762 SCV000209781 uncertain significance not provided 2018-01-26 criteria provided, single submitter clinical testing This variant is denoted ATM c.3299C>T at the cDNA level, p.Thr1100Met (T1100M) at the protein level, and results in the change of a Threonine to a Methionine (ACG>ATG). However, it has been reported as a somatic variant in a bone marrow sample from an individual with chronic myeloid leukemia (Mitani 2016). ATM Thr1100Met was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the beta-adaptin interaction domain (Tavtigian 2009). 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 Thr1100Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000215728 SCV000821846 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000559406 SCV000622405 uncertain significance Ataxia-telangiectasia syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1100 of the ATM protein (p.Thr1100Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. 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: 181993). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Mendelics RCV000559406 SCV000838521 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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.