ArticleHuman mutation2019
Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis.
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Somatic and germline genetic testing pathways in haematological malignancies: Best practice consensus guidelines from the 2025 national meeting organised by UK Cancer Genetics Group (UKCGG), CanGene-CanVar and the NHS England Haematological Oncology Working Group.British journal of haematology · 2026Guideline
- Hereditary Pancreatic Cancer: Genetic Risk, Surveillance Strategies, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Association of gestational choriocarcinoma in a mother and Li-Fraumeni syndrome in her child: The result of a single event?Familial cancer · 2026Article
- Clinical Features and Treatment Strategies of Li-Fraumeni Syndrome Patients With Inherited TP53 Mutations.Molecular genetics & genomic medicine · 2026Article
- Skin cancer risk in hereditary mixed cancer syndromes.Hereditary cancer in clinical practice · 2025Review
- Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice.Journal of medical genetics · 2025Article
- Peripheral blood DNA methylation predicts the early onset of primary tumor in TP53 mutation carriers.Nature communications · 2025Article
- Using large-scale population-based data to improve disease risk assessment of clinical variants.Nature genetics · 2025Review
- Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target.Cancer cell · 2025Article
- Personalized screening strategies forLancet regional health. Americas · 2025Article
- Exploring the Common Mutational Landscape in Cutaneous Melanoma and Pancreatic Cancer.Pigment cell & melanoma research · 2025Review
- Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background.International journal of molecular sciences · 2024Article
- Her2-positive breast cancer in a young patient with Li-Fraumeni syndrome: A comprehensive case study.International journal of surgery case reports · 2024Article
- Current insights and future directions of Li-Fraumeni syndrome.Discover oncology · 2024Review
- Germline variant affecting p53β isoforms predisposes to familial cancer.Nature communications · 2024Article
- Whole-Exome Sequencing Reveals Novel Candidate Driver Mutations and Potential Druggable Mutations in Patients with High-Risk Neuroblastoma.Journal of personalized medicine · 2024Article
- Newborn Screening for Li-Fraumeni Syndrome: Patient Perspectives.Research square · 2024Article
- Phenotype analysis of families with TP53 germline variants at the Center for Familial Breast and Ovarian Cancer, Cologne.Cancer medicine · 2024Article
- Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report.Diagnostic pathology · 2024Article
- Using genomic databases to determine the frequency and population-based heterogeneity of autosomal recessive conditions.Genetics in medicine open · 2024Article
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Abstract
Reports of variable cancer penetrance in Li-Fraumeni syndrome (LFS) have raised questions regarding the prevalence of pathogenic germline TP53 variants. We previously reported higher-than-expected population prevalence estimates in sequencing databases composed of individuals unselected for cancer history. This study aimed to expand and further evaluate the prevalence of pathogenic and likely pathogenic germline TP53 variants in the gnomAD dataset (version r2.0.2, n = 138,632). Variants were selected and classified based on our previously published algorithm and compared with alternative estimates based on three different classification databases: ClinVar, HGMD, and the UMD_TP53 database. Conservative prevalence estimates of pathogenic and likely pathogenic TP53 variants were within the range of one carrier in 3,555-5,476 individuals. Less stringent classification increased the approximate prevalence to one carrier in every 400-865 individuals, mainly due to the inclusion of the controvertible p.N235S, p.V31I, and p.R290H variants. This study shows a higher-than-expected population prevalence of pathogenic and likely pathogenic germline TP53 variants even with the most conservative estimates. However, these estimates may not necessarily reflect the prevalence of the classical LFS phenotype, which is based upon family history of cancer. Comprehensive approaches are needed to better understand the interplay of germline TP53 variant classification, prevalence estimates, cancer penetrance, and LFS-associated phenotype.
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