ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6092C>T (p.Thr2031Ile)

dbSNP: rs1555113613
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 RCV000567229 SCV000665150 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-20 criteria provided, single submitter clinical testing The p.T2031I variant (also known as c.6092C>T), located in coding exon 40 of the ATM gene, results from a C to T substitution at nucleotide position 6092. The threonine at codon 2031 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001228477 SCV001400877 uncertain significance Ataxia-telangiectasia syndrome 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 2031 of the ATM protein (p.Thr2031Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 481045). 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 tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV000567229 SCV002052685 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-10 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 2031 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with colorectal cancer and in unaffected individuals in a colorectal cancer risk study (PMID: 33309985). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV002248782 SCV002517874 uncertain significance not specified 2022-05-04 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.