ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6036A>G (p.Ile2012Met)

dbSNP: rs1591776713
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000821236 SCV000961989 uncertain significance Ataxia-telangiectasia syndrome 2019-11-23 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 2012 of the ATM protein (p.Ile2012Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine.
Ambry Genetics RCV002352456 SCV002658387 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-24 criteria provided, single submitter clinical testing The p.I2012M variant (also known as c.6036A>G), located in coding exon 40 of the ATM gene, results from an A to G substitution at nucleotide position 6036. The isoleucine at codon 2012 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx RCV003325523 SCV004032046 uncertain significance not provided 2023-03-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176)

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