ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Variant classification changes over time in BRCA1 and BRCA2.
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. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis 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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: a systematic review and meta-analysis.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Pooled it
- A Proposed North American Approach for Genetic Testing of Individuals at Risk for Malignant Hyperthermia.Anesthesiology · 2026Article
- A proposed North American approach for genetic testing of individuals at risk for malignant hyperthermia.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2026Review
- Reclassification ofEuropean journal of breast health · 2025Article
- Using large-scale population-based data to improve disease risk assessment of clinical variants.Nature genetics · 2025Review
- [Pathogenic role of CHEK2 variants in Hungarian cancer patients: implications for breast cancer risk and genetic counselling].Magyar onkologia · 2025Article
- Reclassification of VUS inGenetics in medicine open · 2025Article
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- 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
- The Role of Tumor Biomarkers in Tailoring the Approach to Advanced Ovarian Cancer.International journal of molecular sciences · 2024Review
- Guidance for estimating penetrance of monogenic disease-causing variants in population cohorts.Nature genetics · 2024Review
- SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.Database : the journal of biological databases and curation · 2024Article
- Glowing gels and pipettes aplenty: how do commercial stock image banks portray genetic tests?European journal of human genetics : EJHG · 2024Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- Improvement of variant reclassification in genetic neurodevelopmental conditions.Genetics in medicine open · 2024Article
- The importance of variant reinterpretation in inherited cardiovascular diseases: Establishing the optimal timeframe.PloS one · 2024Article
- DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data.Annual review of genomics and human genetics · 2023Review
- Practical considerations for reinterpretation of individual genetic variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Variant curation and interpretation in hereditary cancer genes: An institutional experience in Latin America.Molecular genetics & genomic medicine · 2023Article
- Cases in Precision Medicine: Is There an Obligation to Return Reinterpreted Genetic Results to Former Patients?Annals of internal medicine · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
purposeTo report BRCA1 and BRCA2 (BRCA1/2) variant reassessments and reclassifications between 2012 and 2017 at the Advanced Molecular Diagnostics Laboratory (AMDL) in Toronto, Canada, which provides BRCA1/2 testing for patients in Ontario, and to compare AMDL variant classifications with submissions in ClinVar.
methodsVariants were assessed using a standardized variant assessment tool based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology's guidelines and tracked in an in-house database. Variants were shared through the Canadian Open Genetics Repository and submitted to ClinVar for comparison against other laboratories.
resultsAMDL identified 1209 BRCA1/2 variants between 2012 and 2017. During this period, 32.9% (398/1209) of variants were reassessed and 12.4% (150/1209) were reclassified. The majority of reclassified variants were downgraded (112/150, 74.7%). Of the reclassified variants, 63.3% (95/150) were reclassified to benign, 20.7% (31/150) to likely benign, 10.0% (15/150) to variant of uncertain significance, 2.0% (3/150) to likely pathogenic, and 4.0% (6/150) to pathogenic. Discordant ClinVar submissions were found for 40.4% (488/1209) of variants.
conclusionBRCA1/2 variants may be reclassified over time. Reclassification presents ethical and practical challenges related to recontacting patients. Data sharing is essential to improve variant interpretation, to help patients receive appropriate care based on their genetic results.
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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.