ArticleJCO precision oncology2020
Impact of a Cancer Gene Variant Reclassification Program Over a 20-Year Period.
Article in JCO precision oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- [Hereditary genetic testing and its application in the diagnosis, treatment, and prevention of breast cancer].Magyar onkologia · 2025Guideline
- Real-world genetic testing data of ovarian cancer patients: Informing counseling and risk reduction in patients over age seventy.Gynecologic oncology · 2026Article
- The moderating role of parental cognitive perceptions in the link between children's cancer predisposition genetic testing results and parent psychological adjustment.Journal of pediatric psychology · 2026Article
- Detection rates of multigene panel and exome testing in patients with previous negative BRCA1/2 results.Familial cancer · 2025Article
- Universal Genetic Counseling and Testing for Black Women: A Risk-Stratified Approach to Addressing Breast Cancer Disparities.Clinical breast cancer · 2025Review
- Reclassification of VUS inGenetics in medicine open · 2025Article
- Ethical, legal, and policy dimensions and contentions for reanalysis and reinterpretation of clinical genetic testing results.Frontiers in genetics · 2025Article
- Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer.Frontiers in oncology · 2025Article
- Clinician-Reported Management Recommendations in Response to Universal Germline Genetic Testing in Patients With Prostate Cancer.The Journal of urology · 2024Article
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- Article
- Patterns and Frequency of Pathogenic Germline Variants Among Prostate Cancer Patients Utilizing Multi-Gene Panel Genetic Testing.World journal of oncology · 2024Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand.Journal of personalized medicine · 2023Article
- An Environmental Scan of Consumer-Initiated Germline Genetic Testing for Health Risks.Mayo Clinic proceedings · 2023Review
- An apparent quandary: adoption of polygenics and gene panels for personalised breast cancer risk stratification.BJC reports · 2023Review
- Recontact: a survey of current practices and BRCA1/2 testing in Japan.Journal of human genetics · 2023Article
- The association between age at breast cancer diagnosis and prevalence of pathogenic variants.Breast cancer research and treatment · 2023Article
- Updates in gynecologic care for individuals with lynch syndrome.Frontiers in oncology · 2023Review
- Discordance between germline genetic findings and abnormal tumor immunohistochemistry staining of mismatch repair proteins in individuals with suspected Lynch syndrome.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
purposeHereditary cancer genetic testing can inform personalized medical management for individuals at increased cancer risk. However, many variants in cancer predisposition genes are individually rare, and traditional tools may be insufficient to evaluate pathogenicity. This analysis presents data on variant classification and reclassification over a 20-year period. PATIENTS AND
methodsThis is a retrospective analysis of > 1.9 million individuals who received hereditary cancer genetic testing from a single clinical laboratory (March 1997 to December 2017). Variant classification included review of evidence from traditional tools (eg, population frequency databases, literature) and laboratory-developed tools (eg, novel statistical methods, in-house RNA analysis) by a multidisciplinary expert committee. Variants may have been reclassified more than once and with more than one line of evidence.
resultsIn this time period, 62,842 unique variants were observed across 25 cancer predisposition genes, and 2,976 variants were reclassified. Overall, 82.1% of reclassification events were downgrades (eg, variant of uncertain significance [VUS] to benign), and 17.9% were upgrades (eg, VUS to pathogenic). Among reclassified variants, 82.8% were initially classified as VUS, and 47.5% were identified in ≤ 20 individuals (allele frequency ≤ 0.001%). Laboratory-developed tools were used in 72.3% of variant reclassification events, which affected > 600,000 individuals. More than 1.3 million patients were identified as carrying a variant that was reclassified within this 20-year time period.
conclusionThe variant classification program used by the laboratory evaluated here enabled the reclassification of variants that were individually rare. Laboratory-developed tools were a key component of this program and were used in the majority of reclassifications. This demonstrates the importance of using robust and novel tools to reclassify rare variants to appropriately inform personalized medical management.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.