French‐Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Gene Panel Analysis Through Genotyping or Sequencing in Pharmacogenetics

BACKGROUND: The implementation of pharmacogenetics in clinical practice increasingly relies on multigene panels. OBJECTIVES: The objective of this study is to develop harmonized recommendations for the design and analytical implementation of multigene pharmacogenetic panels, defining clinically relevant genes and associated regions of interest (ROIs) based on evidence strength, therapeutic applicability, and compatibility with genotyping or sequencing technologies. METHODS: The French-Speaking Network of Pharmacogenetics (RNPGx) evaluated 81 candidate genes across five therapeutic domains (i.e., oncology and supportive care, anesthesia and pain management, cardiology, neurology and psychiatry and immunology and infectious diseases) using a structured, evidence-based scoring system. Each gene was evaluated using a 25-point scoring system integrating pharmacogenetic importance, regulatory and professional society recommendations, and expert consensus. For the genes ultimately selected for the core panel, clinically relevant regions of interest were defined and assigned to one of three analytical classes. Class 1 includes variants with established clinical actionability; Class 2 adds optional variants suitable for extended testing in specialized settings; and Class 3 covers broader genomic regions mainly intended for rare variant or structural analyses. RESULTS: A 28-gene core panel was retained. Class 1 included 76 prioritized variants (including CYP2D6 CNV variants), and Class 2 comprised 62 additional variants (with extended analysis for CYP2D6). Class 3 eligibility was retained for 18 genes. CONCLUSION: The RNPGx recommendations offer a harmonized and flexible framework for pharmacogenetic panel design and for the extraction and interpretation of pharmacogenetic data from whole-exome or whole-genome sequencing.