ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2436G>A (p.Met812Ile)

dbSNP: rs876658688
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 RCV000217018 SCV000274280 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-27 criteria provided, single submitter clinical testing The p.M812I variant (also known as c.2436G>A), located in coding exon 15 of the ATM gene, results from a G to A substitution at nucleotide position 2436. The methionine at codon 812 is replaced by isoleucine, an amino acid with highly 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 RCV000627899 SCV000748783 uncertain significance Ataxia-telangiectasia syndrome 2023-07-27 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 812 of the ATM protein (p.Met812Ile). This variant is not present in population databases (gnomAD 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: 230655). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 RCV000217018 SCV001345412 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 812 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 not been reported in individuals affected with ATM-related disorders in the literature. 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.
GeneDx RCV002264920 SCV002546755 uncertain significance not provided 2024-04-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003237345 SCV003936042 uncertain significance Familial cancer of breast 2023-06-06 criteria provided, single submitter clinical testing a variant of unknown significance was detected in the ATM gene (c.2436G>A). This sequence change replaces methionine with isoleucine at codon 812 of the ATM protein (p.Met812Ile). This variant is not present in population databases (ExAC no frequency). In-silico predictions show benign computational verdict based on 10 benign predictions from BayesDel_addAF, DANN, DEOGEN2, EIGEN, LIST-S2, M-CAP, MVP, MutationTaster, PrimateAI and SIFT vs 2 pathogenic predictions from FATHMM-MKL and MutationAssessor and the position is not strongly conserved. This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 230655) with 3 submissions, all of which describe it as of uncertain significance, two stars, no conflicts. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003237345 SCV005055842 uncertain significance Familial cancer of breast 2024-03-25 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.