The Challenge of Genetic Variants of Uncertain Clinical Significance : A Narrative Review.
The Challenge of Genetic Variants of Uncertain Clinical Significance : A Narrative Review.
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具有不确定临床意义的遗传变异的挑战：叙事回顾。
DOI：
10.7326/m21-4109
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发表时间：
2022-07
影响因子：
39.2
通讯作者：
Appelbaum PS
中科院分区：
文献类型：
--
作者：
Burke W;Parens E;Chung WK;Berger SM;Appelbaum PS
基因组检测扩大了诊断和筛查的机会，但也发现了临床意义不确定的遗传变异（VUS）。在以后的重新评估中，只有少数VUS可能被证明是致病性的，但不确定性的解决很少及时。这种不确定性增加了临床决策的复杂性，并可能对患者和医疗保健系统造成伤害和成本，包括解释VUS所需的耗时分析，以及不必要的治疗和不良心理影响的可能性。目前改进变异解释的努力将有助于减少问题的范围，但是人类基因组中罕见和新颖变异的高流行率表明VUS是一个持续的挑战。其他策略可以帮助减轻VUS的潜在危害，包括限制VUS识别或报告的检测方案，根据致病性可能性对VUS进行分类，常规的基于家庭的变异评估，以及加强咨询工作。所有这些都涉及权衡，而适当的平衡措施可能因不同的检测用途和临床环境而异。跨专业审议和公众意见有助于制定系统和广泛支持的管理VUS的政策。
Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUS). Only a minority of VUS are likely to prove to be pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision-making and can result in harms and costs to patients and the healthcare system, including the time-consuming analysis required to interpret a VUS, and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help to reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUS as an ongoing challenge. Additional strategies can help to mitigate the potential harms of VUS, including testing protocols that limit identification or reporting of VUS, subclassifying VUS according to the likelihood of pathogenicity, routine family-based variant evaluation, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUS.
影响因子：
1.9
作者：
Makhnoon S;Mork M;Arun B;Volk RJ;Peterson SK
通讯作者：
Peterson SK