PDF(Pubmed)
Abstract：
Current standards in clinical genetics recognize the need to establish the validity of gene-disease relationships as a first step in the interpretation of sequence variants. We describe our experience incorporating the ClinGen Gene-Disease Clinical Validity framework in our interpretation and reporting workflow for a clinical genome sequencing (cGS) test for individuals with rare and undiagnosed genetic diseases. This \"reactive\" gene curation is completed upon identification of candidate variants during active case analysis and within the test turn-around time by focusing on the most impactful evidence and taking advantage of the broad applicability of the framework to cover a wide range of disease areas. We demonstrate that reactive gene curation can be successfully implemented in support of cGS in a clinical laboratory environment, enabling robust clinical decision making and allowing all variants to be fully and appropriately considered and their clinical significance confidently interpreted.
摘要：
临床遗传学的当前标准认识到需要建立基因-疾病关系的有效性，这是解释序列变异的第一步。我们描述了我们的经验，将ClinGen基因疾病临床有效性框架纳入我们的解释和报告工作流程中，用于罕见和未诊断的遗传疾病个体的临床基因组测序（cGS）测试。这种“反应性”基因策展是在主动病例分析期间和测试周转时间内识别候选变异后完成的，方法是关注最有影响力的证据，并利用框架的广泛适用性来覆盖广泛的疾病领域。我们证明，反应性基因策展可以在临床实验室环境中成功实施，以支持cGS。能够做出稳健的临床决策，并允许所有变体得到充分和适当的考虑，并自信地解释其临床意义。
