Pathogenic missense mutation locations in the Ca²⁺-free thin filament. The atomic model of the regulated cardiac thin filament (PDB accession no. 6kn7; Yamada et al., 2020) is shown, under the low-Ca²⁺ condition of relaxed muscle. Troponin (Tn) and tropomyosin are illustrated in cartoon format, with troponin subunits in pale pink (TnC), purple (TnT), and magenta (TnI) and tropomyosin in black. Actin monomers are in surface format and neutral gray and beige tones. Troponin residues encoded by pathogenic missense mutations are indicated as blue spherical atoms. (A) Troponin sites with pathogenic HCM mutations in dark blue and sites of DCM-inducing substitutions in sky blue. Note the proximity of these sites to the actin-tropomyosin surface. (B) Troponin residues that are sites of variants of uncertain significance are indicated in yellow. They are more widely distributed within troponin, compared with A.