ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8742T>G (p.Ile2914Met)

gnomAD frequency: 0.00001  dbSNP: rs587782264
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130993 SCV000185916 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-23 criteria provided, single submitter clinical testing The p.I2914M variant (also known as c.8742T>G), located in coding exon 59 of the ATM gene, results from a T to G substitution at nucleotide position 8742. The isoleucine at codon 2914 is replaced by methionine, an amino acid with highly similar properties. Another missense alteration at this residue (p.I2914T) has been detected in 1/4112 breast cancer patients and 0/2399 healthy control individuals across numerous studies (Tavtigian S et al. Am. J. Hum. Genet. 2009 Oct;85:427-46). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000130993 SCV000682511 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-07 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 2914 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001363951 SCV001560083 uncertain significance Ataxia-telangiectasia syndrome 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2914 of the ATM protein (p.Ile2914Met). 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: 142142). 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 disruptive. 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.
Baylor Genetics RCV004567126 SCV005057029 uncertain significance Familial cancer of breast 2024-02-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV001363951 SCV002082725 uncertain significance Ataxia-telangiectasia syndrome 2021-10-06 no assertion criteria provided clinical testing

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