Figure 3.

Root decision tree for clinical case report criteria. Case reports are divided into one of three types based on the affected status of the proband, the relevance of the phenotype to the gene in question, and the presence of a known disease etiology. This root decision tree guides the user to the correct detailed decision tree (Supplementary Figures S2–S4) based on these considerations. The variant frequency is an essential lens through which to understand the relevance of case reports. The more frequent a variant is, the more likely it becomes that case reports are simply coincidental.