用于对遗传变异进行分类的知识不断发展,分类可以根据最新可用的数据进行更改。尽管最新的变体分类对于临床管理至关重要,生殖规划,识别有风险的家庭成员,对于如何或在何种情况下进行变异重新解释,各实验室或临床医师之间没有一致的实践.
我们与参与变体重新解释过程的利益相关者进行了探索性焦点小组(N=142)和调查(N=1753)(实验室主任,临床遗传学家,遗传咨询师,非遗传提供者,和患者/父母)评估对关键问题的意见,包括重新解释的开始,要报告的变体,重新解释的责任终止,以及对同意的担忧,成本,和责任。
利益相关者普遍认为,重新解释先前报道的遗传变异的责任不应该有固定的终止点。人们对赔偿责任感到严重关切,并且对变体重新解释的许多后勤方面缺乏共识。
我们的研究结果表明,有必要(1)达成共识和(2)建立透明度和对参与变体重新解释的各方的角色和责任的认识。这些数据为制定变体重新解释指南提供了基础,这些指南可以帮助开发低成本,可扩展,和可访问的方法。
The 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.
We 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.
Stakeholders 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.
Our 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.