ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3439A>G (p.Ile1147Val)

dbSNP: rs769853739
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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 RCV000219347 SCV000276917 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-12 criteria provided, single submitter clinical testing The p.I1147V variant (also known as c.3439A>G), located in coding exon 23 of the ATM gene, results from an A to G substitution at nucleotide position 3439. The isoleucine at codon 1147 is replaced by valine, 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 RCV000557243 SCV000622422 uncertain significance Ataxia-telangiectasia syndrome 2023-08-16 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 1147 of the ATM protein (p.Ile1147Val). This variant is present in population databases (rs769853739, gnomAD 0.0009%). 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: 232715). 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 RCV000219347 SCV001359393 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1147 of the ATM protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251148 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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 RCV001575307 SCV001802271 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Sema4, Sema4 RCV000219347 SCV002536001 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-02 criteria provided, single submitter curation

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