Assigning evidence to actionability: An introduction to variant interpretation in precision cancer medicine
Peter Horak, Jonas Leichsenring, Hannah Goldschmid, Simon Kreutzfeldt, Daniel Kazdal, Veronica Teleanu, Volker Endris, Laura Gieldon, Michael Allgäuer, Anna‐Lena Volckmar, Nicola Dikow, Marcus Renner, Martina Kirchner, Roland Penzel, Carolin Ploeger, Regine Brandt, Huriye Seker‐Cin, Jan Budczies, Christoph E. Heilig, Olaf Neumann, Christian P. Schaaf, Peter Schirmacher, Stefan Fröhling, Albrecht Stenzinger
Abstract
Modern concepts in precision cancer medicine are based on increasingly complex genomic analyses and require standardized criteria for the functional evaluation and reporting of detected genomic alterations in order to assess their clinical relevance. In this article, we propose and address the necessary steps in systematic variant evaluation consisting of bioinformatic analysis, functional annotation and clinical interpretation, focusing on the latter two aspects. We discuss the role and clinical application of current variant classification systems and point out their scope and limitations. Finally, we highlight the significance of the molecular tumor board as a platform for clinical decision-making based on genomic analyses.