Work

A Pilot Meta-Research on Evolving Evidence Behind Genetic Variant (Re)Classification

Year: 2025

Type: book-chapter

Abstract: 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.

Source: Studies in health technology and informatics

DOI: 10.3233/shti250811

Authors: Haotian Ma, Zihan Xu, Wendy Chung, Chunhua Weng, Yifan Peng

Institutions: Weill Cornell Medicine, Boston Children's Hospital, Harvard University, Columbia University

Language: English

Topic: BRCA gene mutations in cancer

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: National Institutes of Health, National Human Genome Research Institute, U.S. National Library of Medicine, National Center for Advancing Translational Sciences