Development and validation of targeted next-generation sequencing panels for detection of germline variants in inherited diseases

Abstract

Context.-The number of targeted next-generation sequencing (NGS) panels for genetic diseases offered by clinical laboratories is rapidly increasing. Before an NGSbased test is implemented in a clinical laboratory, appropriate validation studies are needed to determine the performance characteristics of the test. Objective.-To provide examples of assay design and validation of targeted NGS gene panels for the detection of germline variants associated with inherited disorders. Data Sources.-The approaches used by 2 clinical laboratories for the development and validation of targeted NGS gene panels are described. Important design and validation considerations are examined. Conclusions.-Clinical laboratories must validate performance specifications of each test prior to implementation. Test design specifications and validation data are provided, outlining important steps in validation of targeted NGS panels by clinical diagnostic laboratories.