Proportion of variants with evidence of pathogenicity in hotspot and hotspot+ models
| VUS | Likely pathogenic | Pathogenic | ||||||||||
| N | Sup. (%) | Mod. (%) | Str. (%) | N | Sup. (%) | Mod. (%) | Str. (%) | N | Sup. (%) | Mod. (%) | Str. (%) | |
| Hotspot models | ||||||||||||
| MYH7 | 123 | 10 | 28 | 0 | 93 | 33 | 55 | 0 | 36 | 31 | 61 | 0 |
| MYBPC3 | 97 | 35 | 12 | 0 | 13 | 38 | 23 | 0 | 6 | 33 | 67 | 0 |
| TNNT2 | 19 | 21 | 47 | 0 | 4 | 0 | 50 | 0 | 4 | 0 | 100 | 0 |
| TNNI3 | 18 | 17 | 67 | 0 | 11 | 9 | 91 | 0 | 4 | 0 | 100 | 0 |
| MYL2 | 12 | 25 | 0 | 0 | 1 | 100 | 0 | 0 | 2 | 100 | 0 | 0 |
| MYL3 | 10 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Hotspot+ models | ||||||||||||
| MYH7 | 123 | 18 | 26 | 4 | 93 | 16 | 58 | 14 | 36 | 8 | 75 | 17 |
| MYBPC3 | 97 | 16 | 25 | 7 | 13 | 15 | 54 | 15 | 6 | 17 | 33 | 50 |
| TNNT2 | 19 | 16 | 26 | 16 | 4 | 0 | 50 | 25 | 4 | 0 | 50 | 50 |
| TNNI3 | 18 | 22 | 33 | 22 | 11 | 18 | 45 | 36 | 4 | 0 | 50 | 50 |
| MYL2 | 12 | 0 | 25 | 0 | 1 | 0 | 100 | 0 | 2 | 50 | 50 | 0 |
| MYL3 | 10 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Each observed variant across six genes in our HCM cases was given supporting (OR >10; Sup.), moderate (OR >20; Mod.) or strong (OR >100; Str.) evidence of pathogenicity based on model predictions from the hotspot and hotspot+ models. The proportion of variants with supporting, moderate or strong evidence are stratified by expert classifications made by Oxford Medical Genetics Laboratory.
HCM, hypertrophic cardiomyopathy.