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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Managing Secondary Findings from Germline Pharmacogenomic Testing
Yee Ming Lee1, Elizabeth Kearney2, David F Kisor3
1Independent Researcher, San Diego, CA 92127, USA.
Journal of Personalized Medicine
|July 27, 2026
Summary
Germline pharmacogenomics (PGx) panels often contain genes with secondary findings (SF) unrelated to drug response. Clinical management guidelines are needed for these SF to ensure patient safety and optimize genomic medicine integration.
Area of Science:
- Genomic Medicine
- Clinical Pharmacogenomics
- Translational Genomics
Background:
- Germline pharmacogenomics (PGx) testing is increasingly used in clinical settings.
- These tests can identify secondary findings (SF) related to gene-disease risks, requiring clinical management.
- Current PGx panels vary in content and lack standardized approaches for SF management.
Purpose of the Study:
- To evaluate the content of clinical PGx panels for potential secondary findings (SF).
- To assess the availability of PGx annotations and clinical actionability for genes within these panels.
- To identify the need for standardized frameworks for managing SF from PGx testing.
Main Methods:
- A cross-sectional review of PGx panels from 44 testing sites was conducted.
- Panel content was assessed for PGx annotations, gene-disease validity, clinical actionability, and inclusion in established guidelines (ClinPGx, ClinGen, CPIC, ACMG SF v3.3).
- Genes and variants were analyzed for their PGx relevance and potential SF implications.
Main Results:
- Of 125 genes/alleles/variants analyzed, only 26.4% had PGx annotations.
- A small subset of genes (e.g., CACNA1S, CFTR, G6PD) had actionable SF recommendations based on CPIC and ACMG guidelines.
- Many genes lacked PGx annotations but carried potential SF, necessitating genetic consultation.
Conclusions:
- PGx panels frequently include genes with and without PGx annotations, some posing SF risks.
- There is a critical need for a centralized resource and standardized framework for identifying and managing SF from germline PGx testing.
- The Clinical Genome Resource (ClinGen) PGx Working Group is positioned to lead the development of such a framework.
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