ArticleHuman mutation2009
Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk.
Article in Human mutation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- The association between ATM variants and risk of breast cancer: a systematic review and meta-analysis.BMC cancer · 2021Pooled it
- Polymorphism rs1801516 (G > A) in theThe Journal of international medical research · 2020Pooled it
- ATM rs189037 (G > A) polymorphism increased the risk of cancer: an updated meta-analysis.BMC medical genetics · 2019Pooled it
- Expanding the clinical spectrum of pediatric ataxia-telangiectasia: a case series of novel genetic variants, lupus vulgaris, and hyper-IgM phenotypes.Orphanet journal of rare diseases · 2025Article
- Reclassification of ATM Missense Variants of Uncertain Significance by Integrating Results from Systematic Functional Assays into an ACMG Points-Based Framework.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Missense Mutations inAnimals : an open access journal from MDPI · 2025Article
- Article
- Digenic Inheritance of Mutations in Homologous Recombination Genes in Cancer Patients.Journal of personalized medicine · 2024Article
- ATM Mutations Associate with Distinct Co-Mutational Patterns and Therapeutic Vulnerabilities in NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort.BJUI compass · 2023Review
- Review
- Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India.Scientific reports · 2022Article
- Article
- Review
- BeyondJournal of clinical medicine · 2020Article
- Criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for the Classification of Germline Sequence Variants in Risk Genes for Hereditary Breast and Ovarian Cancer.Geburtshilfe und Frauenheilkunde · 2020Article
- Article
- Childhood-onset autosomal recessive ataxias: a cross-sectional study from Turkey.Neurogenetics · 2020Article
- Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and Mortality in Patients With Non-Small Cell Lung Cancer.JAMA network open · 2019Article
- Phenotypic consequences of somatic mutations in the ataxia-telangiectasia mutated gene in non-small cell lung cancer.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The functional consequences of missense variants are often difficult to predict. This becomes especially relevant when DNA sequence changes are used to determine a diagnosis or prognosis. To analyze the consequences of 12 missense variants in patients with mild forms of ataxia-telangiectasia (A-T), we employed site-directed mutagenesis of ataxia-telangiectasia mutated (ATM) cDNA followed by stable transfections into a single A-T cell line to isolate the effects of each allele on the cellular phenotype. After induction of the transfected cells with CdCl2, we monitored for successful ATM transcription and subsequently assessed: 1) intracellular ATM protein levels; 2) ionizing radiation (IR)-induced ATM kinase activity; and 3) cellular radiosensitivity. We then calculated SIFT and PolyPhen scores for the missense changes. Nine variants produced little or no correction of the A-T cellular phenotype and were interpreted to be ATM mutations; SIFT/PolyPhen scores supported this. Three variants corrected the cellular phenotype, suggesting that they represented benign variants or polymorphisms. SIFT and PolyPhen scores supported the functional analyses for one of these variants (c.1709T>C); the other two were predicted to be "not tolerated" (c.6188G>A and c.6325T>G) and were classified as "operationally neutral." Genotype/phenotype relationships were compared: three deleterious missense variants were associated with an increased risk of cancer (c.6679C>T, c.7271T>G, and c.8494C>T). In situ mutagenesis represents an effective experimental approach for distinguishing deleterious missense mutations from benign or operationally neutral missense variants.
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Registered trials
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