ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6474G>A (p.Met2158Ile)

dbSNP: rs1565511084
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706540 SCV000835597 uncertain significance Ataxia-telangiectasia syndrome 2023-12-18 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 2158 of the ATM protein (p.Met2158Ile). 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: 582463). 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.
Ambry Genetics RCV001025308 SCV001187473 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-29 criteria provided, single submitter clinical testing The p.M2158I variant (also known as c.6474G>A), located in coding exon 44 of the ATM gene, results from a G to A substitution at nucleotide position 6474. The methionine at codon 2158 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is poorly 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 RCV001585659 SCV001821107 uncertain significance not provided 2020-02-28 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000706540 SCV002084363 uncertain significance Ataxia-telangiectasia syndrome 2021-02-02 no assertion criteria provided clinical testing

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