Clinical Germline Genetic Testing Using Paired DNA and RNA Sequencing

This technical report presents findings on the effectiveness of paired DNA and RNA sequencing in clinical germline genetic testing. It outlines the advantages of concurrent testing, particularly in improving the accuracy and detection of pathogenic variants. The report discusses two significant peer-reviewed studies that evaluate the outcomes of such testing, highlighting that splicing variants are more frequently identified when RNA is included in the analysis. It details the impact of RNA evidence on variant classification, noting that nearly half of individuals with RNA-impacted results experienced reclassifications to likely pathogenic or pathogenic. The report also emphasizes the importance of addressing evidence gaps in underrepresented populations, particularly non-White groups, and how paired testing can enhance equity in genetic testing outcomes. Overall, the findings suggest that integrating RNA evidence into genetic testing protocols can lead to better clinical outcomes for patients undergoing hereditary cancer testing.