This study systematically reviewed and synthesized the literature on psychological and clinical outcomes of receiving a variant of uncertain significance (VUS) from multigene panel testing or genomic sequencing. MEDLINE and EMBASE were searched. Two reviewers screened studies and extracted data. Data were synthesized through meta-analysis and meta-aggregation. The search identified 4539 unique studies and 15 were included in the review. Patients with VUS reported higher genetic test–specific concerns on the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale than patients with negative results (mean difference 3.73 [95% CI 0.80 to 6.66] P = 0.0126), and lower than patients with positive results (mean difference −7.01 [95% CI −11.31 to −2.71], P = 0.0014). Patients with VUS and patients with negative results were similarly likely to have a change in their clinical management (OR 1.41 [95% CI 0.90 to 2.21], P = 0.182), and less likely to have a change in management than patients with positive results (OR 0.09 [95% CI 0.05 to 0.19], P < 0.0001). Factors that contributed to how patients responded to their VUS included their interpretation of the result and their health-care provider’s counseling and recommendations. Review findings suggest there may be a need for practice guidelines or clinical decision support tools for VUS disclosure and management.

本研究系统地回顾和综合了关于从多基因面板测试或基因组测序中接受具有不确定意义的变体 (VUS) 的心理和临床结果的文献。检索了 MEDLINE 和 EMBASE。两名评审员筛选研究并提取数据。数据通过荟萃分析和荟萃聚合进行综合。搜索确定了 4539 项独特的研究，其中 15 项被纳入审查。VUS 患者报告对癌症风险评估 (MICRA) 量表的多维影响的基因检测特异性问题高于阴性结果患者（平均差 3.73 [95% CI 0.80 至 6.66] P  = 0.0126），低于阳性患者结果（平均差 -7.01 [95% CI -11.31 至 -2.71]，P = 0.0014)。VUS 患者和阴性结果患者的临床管理相似可能发生变化（OR 1.41 [95% CI 0.90 至 2.21]，P  = 0.182），与阳性结果患者相比，管理变化的可能性较小（OR 0.09 [95% CI 0.05 至 0.19]，P  < 0.0001）。影响患者对 VUS 反应的因素包括他们对结果的解释以及他们的医疗保健提供者的咨询和建议。审查结果表明，可能需要用于 VUS 披露和管理的实践指南或临床决策支持工具。