LAUSR

Abstract One primary challenge in the interpretation of large-scale sequencing studies is the huge number of candidate variants that emerge. This occurs primarily because there are many functional variants in every sequenced genome and because our ability to prioritize variants based on bioinformatic criteria remains limited. Integrating functional characterization of identified mutations with careful genome interpretation can often provide compelling evidence implicating new disease-causing mutations and genes in phenotypically well characterized patients. Here I report progress in identifying pathogenic mutations in large-scale scale studies in epilepsy and other neurodevelopmental diseases. Next I discuss how sequencing is being used to diagnosis rare serious unresolved genetic conditions. Finally, I discuss how the identification of genetic causes of disease can inform treatment choices.