ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5612C>T (p.Thr1871Ile) (rs538452060)

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
Invitae RCV000168364 SCV000219054 uncertain significance Ataxia-telangiectasia syndrome 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1871 of the ATM protein (p.Thr1871Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs538452060, ExAC 0.009%). This variant has been reported in an individual affected with Lynch syndrome-associated cancer and/or colorectal polyps (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 188339). 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 C15"). 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.
Ambry Genetics RCV000221360 SCV000274313 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing Insufficient evidence
GeneDx RCV000236794 SCV000293226 uncertain significance not provided 2017-08-31 criteria provided, single submitter clinical testing This variant is denoted ATM c.5612C>T at the cDNA level, p.Thr1871Ile (T1871I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACC>ATC). This variant has been identified in at least one individual with a Lynch syndrome-associated cancer and/or polyps (Yurgelun 2015). ATM Thr1871Ile was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Thr1871Ile occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Thr1871Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000221360 SCV000911180 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-07 criteria provided, single submitter clinical testing
Mendelics RCV000168364 SCV001138523 uncertain significance Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000236794 SCV001143116 uncertain significance not provided 2018-10-02 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.