PurposeTo describe the frequency and nature of differences in variant classifications between clinicians and genetic testing laboratories.MethodsRetrospective review of variants identified through genetic testing ordered in routine clinical care by clinicians in the Stanford Center for Inherited Cardiovascular Disease. We compared classifications made by clinicians, the testing laboratory, and other laboratories in ClinVar.ResultsOf 688 laboratory classifications, 124 (18%) differed from the clinicians' classifications. Most differences in classification would probably affect clinical care of the patient and/or family (83%, 103/124). The frequency of discordant classifications differed depending on the testing laboratory (P < 0.0001) and the testing laboratory's classification (P < 0.00001). For the majority (82/124, 66%) of discordant classifications, clinicians were more conservative (less likely to classify a variant pathogenic or likely pathogenic). The clinicians' classification was discordant with one or more submitter in ClinVar in 49.1% (28/57) of cases, while the testing laboratory's classification was discordant with a ClinVar submitter in 82.5% of cases (47/57, P = 0.0002).ConclusionThe clinical team disagreed with the laboratory's classification at a rate similar to that of reported disagreements between laboratories. Most of this discordance was clinically significant, with clinicians tending to be more conservative than laboratories in their classifications.

中文翻译：

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临床医生和测试实验室之间变异解释的临床影响差异：单中心经验。

目的描述临床医生和基因检测实验室之间变异分类差异的频率和性质。方法对斯坦福遗传性心血管疾病中心临床医生在常规临床护理中通过基因检测确定的变异进行回顾性审查。我们比较了临床医生、检测实验室和其他实验室在 ClinVar 中所做的分类。结果在 688 个实验室分类中，有 124 个 (18%) 与临床医生的分类不同。大多数分类差异可能会影响患者和/或家庭的临床护理（83%，103/124）。不一致分类的频率因检测实验室 (P < 0.0001) 和检测实验室的分类 (P < 0.00001) 而异。对于大多数人（82/124，66%）的不一致分类中，临床医生更保守（不太可能将变异分类为致病性或可能致病性）。在 49.1% (28/57) 的病例中，临床医生的分类与一名或多名 ClinVar 提交者不一致，而在 82.5% 的病例中，检测实验室的分类与 ClinVar 提交者的分类不一致 (47/57, P = 0.0002)。结论临床团队不同意实验室分类的比例与报告的实验室之间的分歧相似。大多数这种不一致在临床上是显着的，临床医生在分类方面往往比实验室更保守。在 49.1% (28/57) 的病例中，分类与 ClinVar 中的一个或多个提交者不一致，而在 82.5% (47/57, P = 0.0002) 的病例中，检测实验室的分类与 ClinVar 提交者的分类不一致。结论临床团队不同意实验室分类的比率与报告的实验室之间的分歧相似。大多数这种不一致在临床上是显着的，临床医生在分类方面往往比实验室更保守。在 49.1% (28/57) 的病例中，分类与 ClinVar 中的一个或多个提交者不一致，而在 82.5% (47/57, P = 0.0002) 的病例中，检测实验室的分类与 ClinVar 提交者的分类不一致。结论临床团队不同意实验室分类的比率与报告的实验室之间的分歧相似。大多数这种不一致在临床上是显着的，临床医生在分类方面往往比实验室更保守。