Table 1.
Summary of the Genetic Causes of HCM
| Gene | Locus | Protein | Frequency |
|---|---|---|---|
| Myofilament/Sarcomeric HCM | |||
| Giant Filament | |||
| TTN | 2q31 | Titin | Rare |
| Thick Filament | |||
| MYH7 | 14q11.2-q12 | β-Myosin heavy chain | 15–25% |
| MYH6 | 14q11.2-q12 | α-Myosin heavy chain | Rare |
| MYL2 | 12q23-q24.3 | Regulatory myosin light chain | Rare |
| MYL3 | 3p21.2-p21.3 | Essential myosin light chain | Rare |
| Intermediate Filament | |||
| MYBPC3 | 11p11.2 | Cardiac myosin-binding protein C | 15–25% |
| Thin Filament | |||
| TNNT2 | 1q32 | Cardiac troponin T | 3–5% |
| TNNI3 | 19p13.4 | Cardiac troponin I | 1–5% |
| TPM1 | 15q22.1 | α-Tropomyosin | 1–5% |
| ACTC | 15q14 | α-Cardiac actin | Rare |
| TNNC1 | 3p21.1 | Cardiac troponin C | Rare |
| Z-Disc HCM | |||
| ACTN2 | 1q42-q43 | α-Actinin 2 | Rare |
| ANKRD1 | 10q23.31 | Cardiac ankyrin repeat protein | Rare |
| CSRP3 | 11p15.1 | Muscle LIM protein | Rare |
| LBD3 | 10q22.2-q23.3 | LIM binding domain 3 | Rare |
| MYOZ2 | 4q26-q27 | Myozenin 2 | Rare |
| TCAP | 17q12-q21.1 | Telethonin | Rare |
| VCL | 10q22.1-q23 | Vinculin/metavinculin | Rare |
| Calcium-Handling HCM | |||
| CALR3 | 19p13.11 | Calreticulin 3 | Rare |
| CASQ2* | 1p13.3-p11 | Calsequestrin | Rare |
| JPH2 | 20q13.12 | Junctophilin 2 | Rare |
| PLN | 6q22.1 | Phospholamban | Rare |
| RYR2* | 1q43 | Ryanodine receptor 2 | Rare |
| SRI* | 7q21.1 | Sorcin | Rare |
Asterisk indicates additional studies may be needed before accepting as a rare HCM-susceptibility gene. Frequency estimates are derived from a population of all unrelated patients with clinically diagnosed HCM without further clinical refinement based on family history, degree of hypertrophy, age at diagnosis, or septal profile. Rare indicates <1% contribution.