As precision oncology is becoming the norm, genomic analysis of tumors is rapidly guiding clinical decisionmaking. As a result of both more targeted therapeutic options and the recognition of tumor heterogeneity, molecular assessment of tumors is also becoming more comprehensive. But with the identification of increasing numbers of mutations in each tumor, comes the inevitable questioning of whether all of the mutations are in fact pathogenic. Paired-normal testing, comparing tumor mutations to normal tissue from that individual, can help hone in on the alterations that are most likely to be pathogenic. This comparison of tumor and normal samples can also reveal germline variants that hold potential clinical implications for both the patient being tested, as well as his or her family members. Currently, most clinical tumor testing does not currently involve analysis of a matched germline samples, but experts predict that will change in the next few years. While paired testing may not be necessary when assessment is contained to just a few well-characterized mutations, like BRAF, matched testing becomes more important as the scale of sequencing increases. Is Paired Testing Clinically Relevant? When tumors are analyzed without a matched normal comparison sequence, germline variants are detected in the tumor […]