Annotation across protein domains of RYR2 and SCN5A
| Known missense variants | Paralogue mappings | |||||
|---|---|---|---|---|---|---|
| Gene | Protein domains | Pathogenic | Benign | Uncertain | Actual | Enrichment |
| SCN5A | N-terminus | 27 | 2 | 6 | 14 | 0.51 |
| Transmembrane | 277 | 8 | 26 | 355 | 1.57 | |
| Interlinker domains | 99 | 25 | 35 | 41 | 0.31 | |
| C-terminus | 40 | 5 | 16 | 31 | 0.58 | |
| Total | 443 | 40 | 83 | 441 | ||
| RYR2 | Hotspots | 134 | 10 | 17 | 157 | 1.52 |
| Outside hotspots | 20 | 10 | 59 | 118 | 0.69 | |
| Total | 154 | 20 | 76 | 275 | ||
Distribution of known variants and paralogue mutation annotations across protein domains of SCN5A and mutation hotspots of RYR2. There is significant enrichment of both known pathogenic mutations and paralogue mutation mappings in the protein regions recognised to be susceptible to pathogenic variation, that is, the trans-membrane domains of SCN5A and the three mutation hotspots of RYR2.