Table 3. Novel variants found in putative HCM associated genes.
| Gene (GenBank accession No.) | PTADA | Sample ID | Morphology | Het/hom | AA change | Function | Animal model |
Disease association | |
|---|---|---|---|---|---|---|---|---|---|
| Zebrafish | Mouse/Rat | ||||||||
| TTN(NM_001256850) Titin | 9.07E-8 | H56 | A | het | p.Q21058H | Key component of striated muscles assembly and functioning | Abnormal heart contraction, disrupted ventricular cardiac myofibril assembly, pericardial edema78 | Cardiovascular system phenotype79 | HCM30, DCM29 |
| H73 | RC | het | p.L9683P | ||||||
| H41 | N | het | p.L2434H | ||||||
| H04 | N | het | p.E26191V | ||||||
| H04 | N | het | p.L9615I | ||||||
| H27 | A | het | p.P8353L | ||||||
| H19 | A | het | p.R15378C | ||||||
| H29 | A | het | p.K32201N | ||||||
| H59 | S | het | p.E10320X | ||||||
| H36 | S | het | p.P30759A | ||||||
| H14 | A | het | p.F27965fs | ||||||
| RYR2(NM_001035) Ryanodine receptor 2 (cardiac) | 4.73E-4 | H56 | A | het | p.E3809G | Mediate the release of Ca2+ and playing a key role in triggering cardiac muscle contraction | No data | Cardiovascular system phenotype79 | Arrhythmogenic right ventricular dysplasia40, cardiomyopathy41 |
| H68 | A | het | p.R929H | ||||||
| H38 | A | het | c.7966-2A>T | ||||||
| OBSCN(NM_001098623) Obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF | 1.12E-7 | H27 | A | het | p.R5215H | Myofibrils organization | Abnormal heart contraction, abnormal heart structure78 | No data | Cardiomyopathy44 |
| H59 | S | het | p.G7500R | ||||||
| H49 | A | het | p.A996fs | ||||||
| H74 | S | het | p.A1640fs | ||||||
| H40 | S | het | p.A1088fs | ||||||
| H54 | RC | het | p.A1272fs | ||||||
| CMYA5(NM_153610) Cardiomyopathy associated 5 | 2.85E-4 | H13 | RC | het | p.S2813L | Repressor of calcineurin-mediated transcriptional activity | Ventricular hypoplasia, pericardial edema34 | No data | Left ventricular hypertrophy33 |
| H54 | RC | het | p.K1822I | ||||||
| H35 | N | het | p.D3051E | ||||||
| H15 | N | het | p.S2404X | ||||||
| CFLAR(NM_001202518) CASP8 and FADD-like apoptosis regulator | 3.51E-4 | H63 | A | het | p.S135X | Regulation of apoptotic signaling pathway | No data | Failed to survive beyond embryonic day 10.5, impaired heart development50 | Cardiac hypertrophy49 |
| H37 | A | het | p.X367L | ||||||
| MYH15(NM_014981) Myosin, heavy chain 15 | 2.69E-4 | H73 | RC | het | c.3282-1G>T | Muscle contraction | No data | No data | Coronary heart disease47 |
| H03 | A | het | p.R953W | ||||||
| H62 | A | het | p.D337G | ||||||
| H09 | A | het | p.N1732fs | ||||||
| NEB(NM_001164507) Nebulin | 2.56E-4 | H45 | RC | het | c.17634+1G>T | Maintaining the structural integrity of sarcomeres | Abnormal heart contraction, pericardial edema78 | Length maintenance in rat cardiac myocytes48 | Nemaline myopathy82 |
| H36 | S | het | p.Y3985C | ||||||
PTADA indicates P-value generated by the TADA program; ID, identification code; Het/hom, heterozygous or homozygous; HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; AA, amino acid; A, apical hypertrophy; N, neutral septum hypertrophy; S, sigmoid hypertrophy; RC, reverse curvature hypertrophy.