Splice variants represent a significant portion of variants of uncertain significance (VUS) in clinical exome and genome sequencing (ES/GS). However, it is challenging to confirm the impact of these variants by DNA analysis alone due to a lack of functional evidence in RNA splicing. This impacts patients with rare disease, where novel variants are more likely to be classified as VUS. To address this concern, we integrated clinically validated RNA sequencing (RNAseq) into the clinical ES/GS workflow as a reflex test to enhance classification of variants with potential impact on splicing.
