Challenges of variant reinterpretation: Opinions of stakeholders and need for guidelines |
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| Affiliation: | 1. Department of Pediatrics, Columbia University Irving Medical Center, Columbia University, New York, NY;2. Department of Psychiatry, Columbia University Irving Medical Center, Columbia University, New York, NY;3. Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY;4. Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN;5. Department of Pediatrics, Michigan Medicine, Ann Arbor, MI;6. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN;7. Departments of Pediatrics and Human Genetics, University of Michigan Medical School, Michigan Medicine, Ann Arbor, MI;8. Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY;1. Human Genetics and Genetic Counseling Master''s Program, Stanford Medicine, Stanford, CA;2. Stanford Hospitals and Clinics Genetic Testing Optimization Service, Stanford Medicine, Stanford, CA;3. Department of Pathology, Stanford University, Stanford, CA;4. Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA;5. Quantitative Sciences Unit, Stanford University, Palo Alto, CA;1. Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada;2. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada;3. Division of Neonatology, Department of Paediatrics, University of British Columbia, Vancouver, British Columbia, Canada;4. Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, Vancouver, British Columbia, Canada;1. Genomics Education Programme, Health Education England, Birmingham, United Kingdom;2. Bristol Clinical Genetics Service, Department of Clinical Genetics, St Michael’s Hospital, Bristol, United Kingdom;3. Genomics England, London, United Kingdom;4. Wellcome Connecting Science, Wellcome Genome Campus, Cambridge, United Kingdom;1. Department of Health and Kinesiology, Texas A&M University, College Station, TX;2. College of Nursing, Texas A&M University, College Station, TX;3. Department of Nutrition, Texas A&M University, College Station, TX;4. School of Public Health, Texas A&M University, College Station, TX;5. Jeb E. Brooks School of Public Policy, Cornell University, Ithaca, NY;6. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX;7. College of Nursing, Texas A&M University, McAllen, TX;1. Department of Genetics, Cell Biology, and Development, College of Biological Sciences, University of Minnesota, Minneapolis, MN;2. Department of Biology, Macalester College, Saint Paul, MN;3. Libraries, University of Minnesota, Minneapolis, MN;1. The Daffodil Centre, The University of Sydney, A Joint Venture With Cancer Council NSW, Sydney, New South Wales, Australia;2. Inherited Tumour Syndromes Research Group, Cardiff University, Cardiff, Wales, United Kingdom;3. Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands;4. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia;5. Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia;6. Colorectal Medicine & Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia |
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| Abstract: | PurposeThe knowledge used to classify genetic variants is continually evolving, and the classification can change on the basis of newly available data. Although up-to-date variant classification is essential for clinical management, reproductive planning, and identifying at-risk family members, there is no consistent practice across laboratories or clinicians on how or under what circumstances to perform variant reinterpretation.MethodsWe conducted exploratory focus groups (N = 142) and surveys (N = 1753) with stakeholders involved in the process of variant reinterpretation (laboratory directors, clinical geneticists, genetic counselors, nongenetic providers, and patients/parents) to assess opinions on key issues, including initiation of reinterpretation, variants to report, termination of the responsibility to reinterpret, and concerns about consent, cost, and liability.ResultsStakeholders widely agreed that there should be no fixed termination point to the responsibility to reinterpret a previously reported genetic variant. There were significant concerns about liability and lack of agreement about many logistical aspects of variant reinterpretation.ConclusionOur findings suggest a need to (1) develop consensus and (2) create transparency and awareness about the roles and responsibilities of parties involved in variant reinterpretation. These data provide a foundation for developing guidelines on variant reinterpretation that can aid in the development of a low-cost, scalable, and accessible approach. |
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| Keywords: | Genetic testing Liability Variant reclassification Variant reinterpretation Variant of uncertain significance |
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