ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1421G>T (p.Ser474Ile)

dbSNP: rs876659240
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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 RCV000218472 SCV000275477 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-12 criteria provided, single submitter clinical testing The p.S474I variant (also known as c.1421G>T), located in coding exon 9 of the ATM gene, results from a G to T substitution at nucleotide position 1421. The serine at codon 474 is replaced by isoleucine, an amino acid with dissimilar 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 RCV000469416 SCV000546932 uncertain significance Ataxia-telangiectasia syndrome 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 474 of the ATM protein (p.Ser474Ile). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 231580). 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.
GeneDx RCV001799640 SCV002043966 uncertain significance not provided 2021-12-22 criteria provided, single submitter clinical testing Not observed at significant frequency 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
Baylor Genetics RCV003475019 SCV004204435 uncertain significance Familial cancer of breast 2023-10-23 criteria provided, single submitter clinical testing
Natera, Inc. RCV000469416 SCV002095378 uncertain significance Ataxia-telangiectasia syndrome 2021-04-07 no assertion criteria provided clinical testing

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