Table 1.
ICC disease genes (n = 43) categorised by primary disease association and regions not covered at 20× read depth using ICCv2 and NextSeq 500 sequencing
| Cardiac diseases | Core genes | Gene description | Mean callability at 20× coverage (95 % CI) | Base pairs (bp) with <20× read depth |
|---|---|---|---|---|
| Aortopathies | ACTA2 | Actin, alpha 2, smooth muscle, aorta | 100 (100–100) | 0 |
| COL3A1 | Collagen, type III, alpha 1 | 100 (100–100) | 0 | |
| FBN1 | Fibrillin 1 | 100 (100–100) | 0 | |
| MYH11 | Myosin, heavy chain 11, smooth muscle | 100 (100–100) | 0 | |
| TGFB2 | Transforming growth factor, beta 2 | 100 (100–100) | 0 | |
| TGFBR1 | Transforming growth factor, beta receptor 1 | 98.0 (97.8–98.2) | 97 | |
| TGFBR2 | Transforming growth factor, beta receptor II (70/80 kda) | 100 (100–100) | 0 | |
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | DSC2 | Desmocollin 2 | 100 (100–100) | 0 |
| DSG2 | Desmoglein 2 | 100 (100–100) | 0 | |
| DSP | Desmoplakin | 100 (100–100) | 0 | |
| JUP | Junction plakoglobin | 100 (100–100) | 0 | |
| PKP2 | Plakophilin 2 | 100 (100–100) | 0 | |
| Brugada syndrome (BrS) | SCN5A | Sodium channel, voltage-gated, type V, alpha subunit | 100 (100–100) | 0 |
| Catecholaminergic polymorphic ventricular tachycardia (CPVT) | CASQ2 | Calsequestrin 2 (cardiac muscle) | 100 (100–100) | 0 |
| RYR2 | Ryanodine receptor 2 (cardiac) | 100 (100–100) | 0 | |
| Dilated cardiomyopathy (DCM) | DES | Desmin | 100 (100–100) | 0 |
| LMNA | Lamin A/C | 100 (100–100) | 0 | |
| MYBPC3 | Myosin-binding protein C, cardiac | 100 (100–100) | 0 | |
| MYH7 | Myosin, heavy chain 7, cardiac muscle, beta | 100 (99.9–100) | 160 | |
| RBM20 | RNA binding motif protein 20 | 100 (100–100) | 0 | |
| TNNI3 | Troponin I type 3 (cardiac) | 100 (100–100) | 0 | |
| TNNT2 | Troponin T type 2 (cardiac) | 100 (100–100) | 0 | |
| TPM1 | Tropomyosin 1 (alpha) | 100 (100–100) | 0 | |
| TTN | Titin | 99.7 (99.7–99.8) | 1569 | |
| Familial hypercholesterolaemia (FH) | APOB | Apolipoprotein B (including Ag(x) antigen) | 100 (100–100) | 0 |
| LDLR | Low-density lipoprotein receptor | 100 (100–100) | 0 | |
| PCSK9 | Proprotein convertase subtilisin/kexin type 9 | 100 (100–100) | 0 | |
| Hypertrophic cardiomyopathy (HCM) | ACTC1 | Actin, alpha, cardiac muscle 1 | 100 (100–100) | 0 |
| CSRP3 | Cysteine and glycine-rich protein 3 (cardiac LIM protein) | 100 (100–100) | 0 | |
| MYBPC3 | Myosin-binding protein C, cardiac | 100 (100–100) | 0 | |
| MYH7 | Myosin, heavy chain 7, cardiac muscle, beta | 100 (99.9–100) | 160 | |
| MYL2 | Myosin, light chain 2, regulatory, cardiac, slow | 100 (100–100) | 0 | |
| MYL3 | Myosin, light chain 3, alkali; ventricular, skeletal, slow | 100 (100–100) | 0 | |
| TNNI3 | Troponin I type 3 (cardiac) | 100 (100–100) | 0 | |
| TNNT2 | Troponin T type 2 (cardiac) | 100 (100–100) | 0 | |
| TPM1 | Tropomyosin 1 (alpha) | 100 (100–100) | 0 | |
| Long QT syndrome (LQTS) | KCNE1 | Potassium voltage-gated channel, Isk-related family, member 1 | 100 (100–100) | 0 |
| KCNE2 | Potassium voltage-gated channel, Isk-related family, member 2 | 100 (100–100) | 0 | |
| KCNH2 | Potassium voltage-gated channel, subfamily H (eag-related), member 2 | 100 (100–100) | 0 | |
| KCNJ2 | Potassium inwardly rectifying channel, subfamily J, member 2 | 100 (100–100) | 0 | |
| KCNQ1 | Potassium voltage-gated channel, KQT-like subfamily, member 1 | 100 (100–100) | 0 | |
| SCN5A | Sodium channel, voltage-gated, type V, alpha subunit | 100 (100–100) | 0 | |
| Noonan syndrome (NS) | KRAS | V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 100 (100–100) | 0 |
| PTPN11 | Protein tyrosine phosphatase, non-receptor type 11 | 100 (100–100) | 0 | |
| RAF1 | V-raf-1 murine leukemia viral oncogene homolog 1 | 100 (100–100) | 0 | |
| SOS1 | Son of sevenless homolog 1 (Drosophila) | 100 (100–100) | 0 | |
| Phenocopy genes | GLA | Galactosidase, alpha | 100 (100–100) | 0 |
| LAMP2 | Lysosomal-associated membrane protein 2 | 100 (100–100) | 0 | |
| PRKAG2 | Protein kinase, AMP-activated, gamma 2 non-catalytic subunit | 100 (100–100) | 0 |
Genomic coordinates of regions with poor callability are given in Table S7