Clinical Germline Genetic Testing with DNA and RNA Sequencing

This technical report reviews the advancements in clinical germline genetic testing, specifically focusing on the integration of paired DNA and RNA sequencing. The document outlines the significant improvements in accuracy and detection of pathogenic variants achieved through concurrent testing. It presents findings from two major peer-reviewed studies that highlight how RNA evidence enhances the classification of genetic variants, particularly splicing variants that are often missed by DNA-only testing. The report details the impact of RNA evidence on the reclassification of variants of uncertain significance (VUS) and discusses the implications for equity in genetic testing, particularly for non-White populations. The findings indicate that the use of RNA sequencing not only increases the detection of pathogenic variants but also reduces the VUS rate, thereby improving the overall clinical impact on patient outcomes. The report emphasizes the importance of these advancements in addressing health disparities in genetic testing results.