ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
The impact of variant classification on the clinical management of hereditary cancer syndromes.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Automated reanalysis of genomic data for rare disease diagnostics at scale.Nature medicine · 2026Article
- Next-generation sequencing: Driving a paradigm shift from pathogen detection to systems-level analysis.Infectious medicine · 2026Article
- Reclassification ofEuropean journal of breast health · 2025Article
- Electronic Patient Portals as a Modality for Returning Reclassified Genetic Test Results.Molecular genetics & genomic medicine · 2025Article
- [Pathogenic role of CHEK2 variants in Hungarian cancer patients: implications for breast cancer risk and genetic counselling].Magyar onkologia · 2025Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- Ethical, legal, and policy dimensions and contentions for reanalysis and reinterpretation of clinical genetic testing results.Frontiers in genetics · 2025Article
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- The importance of variant reinterpretation in inherited cardiovascular diseases: Establishing the optimal timeframe.PloS one · 2024Article
- Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer.Human genomics · 2023Article
- Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study.Journal of community genetics · 2023Article
- Practices and Views of US Oncologists and Genetic Counselors Regarding Patient Recontact After Variant Reclassification: Results of a Nationwide Survey.JCO precision oncology · 2023Article
- Article
- How should we address the inevitable harms from non-negligent variant reclassification in predictive genetic testing?Journal of genetic counseling · 2023Article
- BRCA1 Norway: comparison of classification for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories.Familial cancer · 2022Article
- A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.International journal of molecular sciences · 2022Article
- Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes.Nature communications · 2022Article
- Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository.Journal of medical genetics · 2022Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe reclassification of genetic variants poses a significant challenge for laboratories and clinicians. Variant review has resulted in the reclassification of variants of unknown significance as well as the reclassification of previously established pathogenic and likely pathogenic variants. These reclassifications have the potential to alter the clinical management of patients with hereditary cancer syndromes.
methodsResults were reviewed for 1694 patients seen for hereditary cancer evaluation between August 2012 and May 2017 to determine the frequency and types of variant reclassification. Patients with reclassifications with high potential for impact were monitored for alterations in organ surveillance, prophylactic surgery, and cascade testing.
resultsOne hundred forty-two variants were reclassified representing 124/1694 (7.3%) patients; 11.3% of reclassifications (16/142) had a high potential for clinical impact with 94% (15/16) altering clinical management of patients with 56% (9/16) changing multiple areas of management.
conclusionWhile reclassifications are rare, the impact on clinical management is profound. In many cases, patients with downgraded pathogenic/likely pathogenic variants had years of unnecessary organ surveillance and underwent unneeded surgical intervention. In addition, cascade testing misidentified those at risk for developing cancers, thereby altering the management across generations. The frequency and types of alterations to clinical management highlight the need for timely variant reclassification.
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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.