ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3353C>T (p.Thr1118Ile)

dbSNP: rs539847847
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000466800 SCV000546806 uncertain significance Ataxia-telangiectasia syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1118 of the ATM protein (p.Thr1118Ile). This variant is present in population databases (rs539847847, 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: 407537). 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 RCV000771872 SCV000904603 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 1118 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. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has been identified in 1/250952 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.
Mendelics RCV000466800 SCV001138486 uncertain significance Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000771872 SCV001181497 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-15 criteria provided, single submitter clinical testing The p.T1118I variant (also known as c.3353C>T), located in coding exon 22 of the ATM gene, results from a C to T substitution at nucleotide position 3353. The threonine at codon 1118 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly 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.
GeneDx RCV001764395 SCV002000186 uncertain significance not provided 2020-10-21 criteria provided, single submitter clinical testing Not observed at a 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
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003227752 SCV003925066 uncertain significance Familial cancer of breast 2023-05-17 criteria provided, single submitter clinical testing A variant of uncertain significance was detected in the ATM gene (p.Thr1118Ile).This sequence change replaces Threonine, which is neutral and polar, with Isoleucine, which is neutral and non-polar, at codon 1118 of the ATM protein (p.Thr1118Ile). This variant is present in population databases (rs539847847, 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: 407537). This amino acid position is poorly conserved ( PhyloP=1.4) . In addition, this alteration is predicted to be tolerated by in silico analysis. 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. Heterozygous pathogenic/likely pathogenic mutations is the ATM gene cause susceptibility to breast cancer (OMIM# 114480).
Baylor Genetics RCV003227752 SCV004210073 uncertain significance Familial cancer of breast 2023-08-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000466800 SCV002082362 uncertain significance Ataxia-telangiectasia syndrome 2021-05-18 no assertion criteria provided clinical testing

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