Ma Haotian, Xu Zihan, Chung Wendy, Weng Chunhua, Peng Yifan
Weill Cornell Medicine, New York, NY, US.
Boston Children's Hospital and Harvard Medical School, Boston, MA, US.
Stud Health Technol Inform. 2025 Aug 7;329:108-112. doi: 10.3233/SHTI250811.
Variant classification and reclassification are fundamental to advancing precision medicine. This study focuses on the reclassifications of variants of uncertain significance (VUS) in BRCA1 and BRCA2 genes. By analyzing 162 unique cited publications supporting VUS reclassifications, we examined the accuracy, completeness, and currency of citations to these publications. Our findings reveal missing or inadequate evidence for reclassifications, as well as temporally misaligned citations and ClinVar submissions. Furthermore, we observed patterns in the cited studies, including the use of classification recommendations, genetic mechanisms, computational tools, and diverse population studies. This study underscores the need for stronger evidence supporting reclassifications and greater inclusion of diverse populations to optimize genomic variant reclassification and clinical decision-making.
变异分类和重新分类是推进精准医学的基础。本研究聚焦于BRCA1和BRCA2基因中意义未明变异（VUS）的重新分类。通过分析支持VUS重新分类的162篇独特引用文献，我们检验了这些文献引用的准确性、完整性和时效性。我们的研究结果揭示了重新分类存在证据缺失或不足的情况，以及时间上不一致的引用和向ClinVar提交的数据。此外，我们观察到了引用研究中的模式，包括分类建议的使用、遗传机制、计算工具和多样化的人群研究。本研究强调需要更有力的证据支持重新分类，并更多纳入多样化人群，以优化基因组变异重新分类和临床决策。
