On the verge of diagnosis: Detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing

The variable evidence supporting gene–disease associations contributes to the difficulty of accurate variant reporting in a clinical setting. An evidence-based scoring system for evaluating the clinical validity of gene–disease associations, proposed by ClinGen, considers experimental as well as genetic evidence. De novo variants are heavily weighted, given the overall rarity in the genome and their contribution to human disease, however they...