Managing Secondary Findings from Germline Pharmacogenomic Testing.

Background/Objectives: Germline pharmacogenomics (PGx) testing performed by clinical laboratories and companies can reveal secondary findings (SF) related to gene-disease risk that clinicians must appropriately manage. This study evaluated PGx panel content for potential SF using the Clinical Pharmacogenomics (ClinPGx) resource, the Clinical Genome Resource (ClinGen), and the American College of Medical Genetics and Genomics (ACMG). Methods: A cross-sectional review of PGx panels offered by laboratories and companies was assessed for ClinPGx PGx annotation, ClinGen's gene-disease validity and clinical actionability classifications, Clinical Pharmacogenetics Implementation Consortium (CPIC) incidental finding (IF) comments, and ACMG SF v3.3 inclusion. Results/Discussion: Forty-four testing sites provided panel content, yielding 125 genes, alleles, and variants. Of these, 26.4% (33/125) had PGx annotations while 73.6% (92/125) did not. A small subset of genes-CACNA1S, CFTR, G6PD, LDLR, MT-RNR1, and RYR1-had actionable recommendations based on CPIC and ACMG. Additional genes such as ATM, F5, ITGB3, and SCN1A may require consultation with genetics professionals. These findings underscore the need for a centralized resource for identifying gene-specific SF from germline PGx testing and guidance on their clinical management. Conclusions: PGx panels often include genes with and without established PGx annotations, some of which have potential SF implications. ClinGen's PGx Working Group, which aims to integrate PGx into the broader context of genomic medicine, may be well-positioned to facilitate the development of a standardized framework for managing potential SF from panel-based PGx testing as the field evolves.