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.

中文翻译：

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变异重新分类对心血管遗传学临床环境的影响

心血管疾病 (CVD) 的基因检测在过去十年中取得了进展，但这些进展对变异分类提出了新的挑战。为了应对这些挑战，ACMG/AMP 于 2015 年发布了变异解释指南。本研究旨在确定这些指南对临床心血管遗传学中的变异分类有何影响。一项回顾性图表审查确定了接受临床基因检测并在与 CVD 相关的基因中发现变异的患者。对于每个变体，都进行了系统证据审查，并应用 ACMG 指南进行分类。这些分类与患者基因检测报告中提供的分类进行了比较。该研究在 237 名患者中鉴定了 223 个独特的变异。79 个 (35%) 变体的分类与其临床报告不同。这些重新分类中有 28 次 (35%) 会改变 38 名患者的医疗管理建议。这些指南的应用导致本研究中大约三分之一的变体被重新分类。临床医生可以在变异分类过程中发挥更积极的作用。由于重新分类可能对临床筛查建议产生影响，因此在临床 CVD 环境中应随着时间的推移更新变异分类。临床医生可以在变异分类过程中发挥更积极的作用。由于重新分类可能对临床筛查建议产生影响，因此在临床 CVD 环境中应随着时间的推移更新变异分类。临床医生可以在变异分类过程中发挥更积极的作用。由于重新分类可能对临床筛查建议产生影响，因此在临床 CVD 环境中应随着时间的推移更新变异分类。