Vears Danya F, Sénécal Karine, Borry Pascal
Centre for Biomedical Ethics and Law, Department of Public Health and Primary Care, KU Leuven - University of Leuven, Leuven, Belgium; Leuven Institute for Human Genomics and Society, KU Leuven - University of Leuven, Belgium.
Centre of Genomics and Policy, McGill University, Montreal, Quebec, Canada.
Eur J Med Genet. 2017 Oct;60(10):553-558. doi: 10.1016/j.ejmg.2017.07.016. Epub 2017 Aug 1.
The nature of next generation sequencing technologies (NGS) results in the generation of large amounts of data and the identification of numerous variants, for some of which the clinical significance may be difficult to ascertain based on our current knowledge. These Variants of Uncertain Significance (VUS) may be identified in genes in which the function is known or unknown and which may or may not be related to the original rationale for sequencing the patient. Little is known about whether laboratories report VUS to clinicians and current guidelines issued by some of the most notable professional bodies do not provide specific recommendations on this point. To address this, 26 interviews were conducted with 27 laboratory personnel, representing 24 laboratories in Europe (12), Canada (5) and Australasia (7) in order to explore their reporting practices. Participants highlighted that the classification of variants is a real challenge despite the presence of classification guidelines. We identified variation in the reporting practices of VUS across the laboratories within the study. While some laboratories limit their reporting to variants that are pathogenic and thought to be causative of the phenotype, more commonly laboratories report VUS when they are identified in genes related to the clinical question. Some laboratories will also report VUS in candidate genes. VUS that are secondary findings are generally not reported. While it is unclear whether uniformity in reporting is desirable, exploring the perspectives of laboratory personnel undertaking these analyses are critical to ensure the feasibility of any future reporting recommendations.
下一代测序技术（NGS）的特性导致产生大量数据并识别出众多变异，其中一些变异的临床意义基于我们目前的知识可能难以确定。这些意义未明的变异（VUS）可能在功能已知或未知的基因中被识别，且这些基因可能与或可能不与对患者进行测序的原始理由相关。对于实验室是否向临床医生报告VUS知之甚少，一些最著名的专业机构发布的现行指南在这一点上并未提供具体建议。为了解决这个问题，我们对27名实验室人员进行了26次访谈，他们代表了欧洲（12个）、加拿大（5个）和澳大拉西亚（7个）的24个实验室，以探讨他们的报告做法。参与者强调，尽管有分类指南，但变异的分类仍是一项真正的挑战。我们在研究中的各实验室之间发现了VUS报告做法的差异。虽然一些实验室将报告限制在被认为是致病的且被认为是表型病因的变异上，但更常见的情况是，当在与临床问题相关的基因中识别出VUS时，实验室会进行报告。一些实验室也会报告候选基因中的VUS。作为次要发现的VUS通常不会被报告。虽然尚不清楚报告的一致性是否可取，但探索进行这些分析的实验室人员的观点对于确保未来任何报告建议的可行性至关重要。
