ArticleThe Journal of clinical endocrinology and metabolism2018
p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer.
Article in The Journal of clinical endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Consideration of inherited cancer risk on a continuum: An international and multidisciplinary perspective: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2026Guideline
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Expert consensus on the reporting and clinical follow up of individuals with incidentally discovered germline RET variants in the UK.Endocrine-related cancer · 2026Article
- RET Lys666Asn has a low rate of MEN2-related tumors but may be associated with pheochromocytoma.Hormones (Athens, Greece) · 2026Article
- From clinical genetics to genomic-based public health screening programmes: duty-based ethics as a guide for responsible implementation.European journal of human genetics : EJHG · 2026Article
- Specification of frequency criteria for secondary findings genes to improve variant classification concordance.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Geospatial inheritance across the breath of the RET mutational landscape of multiple endocrine neoplasia 2A.Endocrine · 2025Article
- Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice.Journal of medical genetics · 2025Article
- Medullary Thyroid Cancer Risk and Mortality in Carriers of Incidentally Identified MEN2A RET Variants.JAMA network open · 2025Article
- Genomic testing for RET in the clinic: UK and global perspective.Endocrine-related cancer · 2025Review
- Hereditary Medullary Thyroid Cancer: Genotype-Phenotype Correlation.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Guidance for estimating penetrance of monogenic disease-causing variants in population cohorts.Nature genetics · 2024Review
- Epigenetics in thyroid cancer: a bibliometric analysis.Endocrine connections · 2024Article
- Two sisters diagnosed with familial paraganglioma syndrome type 1 (FPGL1) and multiple endocrine neoplasia type 2A (MEN2A).World journal of surgical oncology · 2024Article
- Medullary Thyroid Cancer: Updates and Challenges.Endocrine reviews · 2023Article
- Risk-reducing surgery for individuals with cancer-predisposing germline pathogenic variants and no personal cancer history: a review of current UK guidelines.British journal of cancer · 2023Review
- The Spectrum of Germline Nucleotide Variants in Gastric Cancer Patients in the Kyrgyz Republic.Current issues in molecular biology · 2023Article
- Thyroidectomy Outcomes in Patients Identified With RET Pathogenic Variants Through a Population Genomic Screening Program.JAMA otolaryngology-- head & neck surgery · 2023Article
- Genetics of monogenic disorders of calcium and bone metabolism.Clinical endocrinology · 2022Review
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Abstract
Context: To date, penetrance figures for medullary thyroid cancer (MTC) for variants in rearranged during transfection (RET) have been estimated from families ascertained because of the presence of MTC. Objective: To gain estimates of penetrance, unbiased by ascertainment, we analyzed 61 RET mutations assigned as disease causing by the American Thyroid Association (ATA) in population whole-exome sequencing data. Design: For the 61 RET mutations, we used analyses of the observed allele frequencies in ∼51,000 individuals from the Exome Aggregation Consortium (ExAC) database that were not contributed via The Cancer Genome Atlas (TCGA; non-TCGA ExAC), assuming lifetime penetrance for MTC of 90%, 50%, and unbounded. Setting: Population-based. Results: Ten of 61 ATA disease-causing RET mutations were present in the non-TCGA ExAC population with observed frequency consistent with penetrance for MTC of >90%. For p.Val804Met, the lifetime penetrance for MTC, estimated from the allele frequency observed, was 4% [95% confidence interval (CI), 0.9% to 8%]. Conclusions: Based on penetrance analysis in carrier relatives of p.Val804Met-positive cases of MTC, p.Val804Met is currently understood to have high-lifetime penetrance for MTC (87% by age 70), albeit of later onset of MTC than other RET mutations. Given our unbiased estimate of penetrance for RET p.Val804Met of 4% (95% CI, 0.9% to 8%), the current recommendation by the ATA of prophylactic thyroidectomy as standard for all RET mutation carriers is likely inappropriate.
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