Figure 4
Comparison of the number of variants reported as putatively pathogenic in research studies. Hypertrophic cardiomyopathy (HCM) (a) and dilated cardiomyopathy (DCM) (b) in research studies (using generic analysis criteria such as variant class, missense-effect predictions, and variant population frequency in the Exome Sequencing Project) with those predicted as pathogenic by the excess of variation in cases over Exome Aggregation Consortium (ExAC) in each gene. For the HCM study14 (a), genes are colored according to the cardiac disease for which they are primarily associated, as defined by Lopes et al.14 Although there is good concordance between the research findings and the ExAC predictions for established HCM genes, for genes primarily associated with DCM, ARVC, and arrhythmias, the variation in cases is similar to that in ExAC. In the DCM study15,16,17 (b), variation burden in MYBPC3, SCN5A, and MYH6 is similar between the published research cases and ExAC, suggesting that most variants in these genes are unlikely to cause DCM.
