Guidelines. High throughput sequencing generates an unprecedented amount of genetic data. Most exomes are generated in a specific context, i.e. the genetic data is screened for variations in specific candidate genes or screened for de novo mutations. However, these approaches only use a small fraction of the genetic data generated per individual. High-throughput sequencing may also reveal clues towards possibly relevant diseases, and there is an ongoing debate if and how incidental findings should be returned to individuals undergoing high-throughput sequencing. Now, a recent paper in the American Journal of Human Genetics uses a very stringent clinical approach to assess the frequency of medically actionable findings in exome data. The results are not what you would think, and there is an urgent need to fix the existing databases. Continue reading