PurposeEfforts have been made by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology to make variant classification more uniform, but many limitations remain. Reclassification of a variant of uncertain significance (VUS) is expected, but other more certain calls, like pathogenic or benign, can also be reclassified once additional information is gathered. Variant reclassification can create difficult circumstances for both patients and clinicians.MethodsRetrospective review of all variant reclassifications in genes associated with hereditary cancer syndromes at one clinic between September 2013 and February 2017 was completed. All variant reclassifications were completed and reported by the original testing laboratory.ResultsA total of 1,103 hereditary cancer tests were ordered. Fewer than 5% (40/1,103) of the initial reports were updated during that time period. Most reclassifications (29/40) were downgrades of VUS to likely benign. Only three reclassifications could potentially alter medical management.ConclusionThe majority of variant reclassifications do not impact medical management. Upgrading a variant call to pathogenic could be important for a patient's care and shows the importance of open communication between laboratories and clinicians. A variant downgrade from pathogenic can be a significant reclassification as well, especially if prophylactic surgery has been completed.

中文翻译：

---

在遗传性癌症诊所观察到变异重新分类的频率和挑战。

目的美国医学遗传学和基因组学学院和分子病理学协会已努力使变异分类更加统一，但仍然存在许多限制。对不确定意义的变体 (VUS) 进行重新分类是预期的，但是一旦收集到更多信息，也可以重新分类其他更确定的调用，如致病性或良性。变异重新分类会给患者和临床医生带来困难。方法完成了对 2013 年 9 月至 2017 年 2 月期间在一家诊所中与遗传性癌症综合征相关基因的所有变异重新分类的回顾性审查。所有变异重新分类均由原始检测实验室完成并报告。结果共订购了 1,103 项遗传性癌症检测。少于 5% (40/1, 103) 的初始报告在此期间进行了更新。大多数重新分类 (29/40) 将 VUS 降级为可能是良性的。只有三个重新分类可能会改变医疗管理。结论大多数变体重新分类不影响医疗管理。将变异调用升级为致病性可能对患者的护理很重要，并显示了实验室和临床医生之间开放式沟通的重要性。从致病性降级的变异也可能是一个重要的重新分类，特别是如果预防性手术已经完成。结论大多数变异重新分类不影响医疗管理。将变异调用升级为致病性可能对患者的护理很重要，并显示了实验室和临床医生之间开放式沟通的重要性。从致病性降级的变异也可能是一个重要的重新分类，特别是如果预防性手术已经完成。结论大多数变异重新分类不影响医疗管理。将变异调用升级为致病性可能对患者的护理很重要，并显示了实验室和临床医生之间开放式沟通的重要性。从致病性降级的变异也可能是一个重要的重新分类，特别是如果预防性手术已经完成。