Division of Human Genetics, The Ohio State University, Columbus, OH, USA.
Department of Clinical Genetics, Northwestern Medicine Central DuPage Hospital, Winfield, IL, USA.
J Genet Couns. 2021 Apr;30(2):503-512. doi: 10.1002/jgc4.1336. Epub 2020 Oct 7.
Genetic testing for cardiovascular disease (CVD) has advanced over the past ten years, but these advancements have posed new challenges in variant classification. To address these challenges, ACMG/AMP published guidelines for variant interpretation in 2015. This study aimed to determine what impact these guidelines have on variant classification in clinical cardiovascular genetics. A retrospective chart review identified patients who underwent clinical genetic testing and had a variant identified in a gene associated with CVD. For each variant, systematic evidence review was performed and ACMG guidelines were applied for classification. These classifications were compared to those provided on patients' genetic test reports. This study identified 223 unique variants in 237 patients. Seventy-nine (35%) of the variants had classifications that differed from their clinical reports. Twenty-eight (35%) of these reclassifications would have changed medical management recommendations for 38 patients. Application of these guidelines resulted in reclassification for approximately one-third of the variants in this study. Clinicians can have a more active role in the process of variant classification. Variant classifications should be updated over time in the clinical CVD setting due to the impact reclassifications can have on clinical screening recommendations.
在过去的十年中，心血管疾病 (CVD) 的基因检测取得了进展，但这些进展给变异分类带来了新的挑战。为了应对这些挑战，ACMG/AMP 于 2015 年发布了变异解读指南。本研究旨在确定这些指南对临床心血管遗传学中变异分类的影响。回顾性图表审查确定了接受临床基因检测且在与 CVD 相关基因中发现变异的患者。对每个变异进行系统证据审查，并应用 ACMG 指南进行分类。将这些分类与患者基因检测报告中的分类进行比较。本研究在 237 名患者中确定了 223 个独特的变异。79 个（35%）变异的分类与临床报告不同。其中 28 个（35%）重新分类将改变 38 名患者的医疗管理建议。应用这些指南使该研究中约三分之一的变异重新分类。临床医生可以在变异分类过程中发挥更积极的作用。由于重新分类对临床筛查建议的影响，在临床 CVD 环境中，变异分类应随着时间的推移进行更新。
