多基因panel 及基因组检测中报告的 VUS 景观：是时候改变了。
The landscape of reported VUS in multi-gene panel and genomic testing: Time for a change.
机构信息
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA; Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA; Pathology, Harvard Medical School, Boston, MA.
Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO; Department of Pediatrics, School of Medicine, University of Missouri, Kansas City, MO; Genomic Medicine Center, Children's Mercy Hospital, Kansas City, MO.
出版信息
Genet Med. 2023 Dec;25(12):100947. doi: 10.1016/j.gim.2023.100947. Epub 2023 Jul 30.
PURPOSE
Variants of uncertain significance (VUS) are a common result of diagnostic genetic testing and can be difficult to manage with potential misinterpretation and downstream costs, including time investment by clinicians. We investigated the rate of VUS reported on diagnostic testing via multi-gene panels (MGPs) and exome and genome sequencing (ES/GS) to measure the magnitude of uncertain results and explore ways to reduce their potentially detrimental impact.
METHODS
Rates of inconclusive results due to VUS were collected from over 1.5 million sequencing test results from 19 clinical laboratories in North America from 2020 to 2021.
RESULTS
We found a lower rate of inconclusive test results due to VUSs from ES/GS (22.5%) compared with MGPs (32.6%; P < .0001). For MGPs, the rate of inconclusive results correlated with panel size. The use of trios reduced inconclusive rates (18.9% vs 27.6%; P < .0001), whereas the use of GS compared with ES had no impact (22.2% vs 22.6%; P = ns).
CONCLUSION
The high rate of VUS observed in diagnostic MGP testing warrants examining current variant reporting practices. We propose several approaches to reduce reported VUS rates, while directing clinician resources toward important VUS follow-up.
目的
意义未明的变异（VUS）是诊断性基因检测的常见结果，可能由于潜在的误解和下游成本而难以管理，包括临床医生的时间投入。我们调查了通过多基因panel（MGPs）和外显子组和基因组测序（ES/GS）进行诊断性检测报告的 VUS 发生率，以衡量不确定结果的程度，并探索降低其潜在不利影响的方法。
方法
从 2020 年至 2021 年，我们从北美 19 个临床实验室的超过 150 万份测序测试结果中收集了由于 VUS 而导致的不确定结果的发生率。
结果
我们发现 ES/GS（22.5%）导致的不确定测试结果的发生率低于 MGPs（32.6%；P<.0001）。对于 MGPs，不确定结果的发生率与panel 大小相关。使用三联体降低了不确定的发生率（18.9% vs 27.6%；P<.0001），而与 ES 相比，使用 GS 没有影响（22.2% vs 22.6%；P=ns）。
结论
在诊断性 MGP 检测中观察到的高 VUS 发生率需要检查当前的变异报告实践。我们提出了几种方法来降低报告的 VUS 发生率，同时指导临床医生资源进行重要的 VUS 随访。
Zotero 插件