ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.430A>G (p.Ile144Val)

dbSNP: rs1555059323
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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 RCV000535806 SCV000622489 uncertain significance Ataxia-telangiectasia syndrome 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 144 of the ATM protein (p.Ile144Val). 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: 453513). 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.
Color Diagnostics, LLC DBA Color Health RCV001186966 SCV001353589 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-21 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 144 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. In a large international case-control study, this variant was reported in 1/60466 breast cancer cases and absent in 53461 controls (PMID: 33471991). 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.
Ambry Genetics RCV001186966 SCV002626777 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-24 criteria provided, single submitter clinical testing The p.I144V variant (also known as c.430A>G), located in coding exon 4 of the ATM gene, results from an A to G substitution at nucleotide position 430. The isoleucine at codon 144 is replaced by valine, an amino acid with highly similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). This amino acid position is 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.
Natera, Inc. RCV000535806 SCV002091567 uncertain significance Ataxia-telangiectasia syndrome 2021-06-23 no assertion criteria provided clinical testing

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