Figure 2. Location of Ryanodine Receptor 2 (RyR2) Sequence Variants in the 3-Dimensional (3-D) Structure of RyR2.

A, Schematic diagram of the linear sequence of RyR2 showing major structural domains of RyR2 (blue boxes). Orange boxes indicate 4 disease-associated variant clusters (variant hotspots). RyR2 variants identified and characterized in this study are indicated beneath their corresponding domains. B, Locations of RyR2 variants in the 3-D structure of RyR2 (Protein Data Bank identification code 6JI0). Locations of the cytosolic calcium ion (Ca²⁺) binding sites, U-motif, C-terminal domain (CTD), S2 to S3 loop, and S1 to S6 helixes are also depicted. The 3-D locations of RyR2 residues, Q2275 and E4451, have not been resolved; therefore, the p.Q2275H and p.E4451del variants are not shown in the 3-D structure.