A plot twist: When RNA evidence challenges our expectations of DNA results

Paired DNA and RNA testing (DGT-RGT) improves accuracy of DNA results by detecting spliceogenic variants that reside outside of standard next generation sequence (NGS) capture and by providing a functional line of evidence in variant classification. An additional benefit of DGT-RGT is the identification of variants that cause unanticipated or unconventional splicing events. Here we present a variant-level case series highlighting unexpected RNA findings identified at one clinical diagnostic laboratory through DGT-RGT.