ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4210A>G (p.Ile1404Val)

gnomAD frequency: 0.00001  dbSNP: rs786201832
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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 RCV000164320 SCV000214951 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-30 criteria provided, single submitter clinical testing The p.I1404V variant (also known as c.4210A>G), located in coding exon 27 of the ATM gene, results from an A to G substitution at nucleotide position 4210. The isoleucine at codon 1404 is replaced by valine, an amino acid with highly similar properties. This alteration was detected on a 25-gene panel test in an African woman who was diagnosed with breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33). 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 RCV000702252 SCV000831099 uncertain significance Ataxia-telangiectasia syndrome 2024-09-17 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 1404 of the ATM protein (p.Ile1404Val). This variant is present in population databases (rs786201832, gnomAD 0.007%). 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: 184971). 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.
Baylor Genetics RCV004567240 SCV005057081 uncertain significance Familial cancer of breast 2024-01-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000164320 SCV006064882 uncertain significance Hereditary cancer-predisposing syndrome 2025-03-11 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1404 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 1/250752 chromosomes 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.
Natera, Inc. RCV000702252 SCV002079280 uncertain significance Ataxia-telangiectasia syndrome 2020-11-06 no assertion criteria provided clinical testing

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