Table 2. Distribution within troponin of apparently tolerated mutation sites from gnomAD v2.
| Troponin subunit or subunit region | Sites without VUS or pathogenic substitution | Sites with gnomAD alleles only | Density of sites with gnomAD alleles only (%) | P vs. troponin (or P vs. troponin without TnC N-lobe) | |
|---|---|---|---|---|---|
| Troponin | |||||
| All | TnI, TnT, TnC | 563 | 171 | 30.4 | |
| All except TnC | TnI, TnT | 406 | 133 | 32.8 | |
| All except TnC N-lobe | TnC86–161, TnI, TnT | 478 | 162 | 33.9 | |
| Unseen by Cryo-EM | (See legend) | 167 | 68 | 40.7 | 0.0004 (0.014) |
| TnI | |||||
| All | 1–210 | 165 | 57 | 34.5 | NS (NS) |
| N 2/3 | 1–136 | 124 | 50 | 40.3 | 0.005 (NS) |
| C 1/3 | 137–210 | 41 | 7 | 17.1 | 0.036 (0.011) |
| TnT | |||||
| All | 1–288 | 241 | 76 | 31.5 | NS (NS) |
| Cryo-EM tail helix | 87–150 | 48 | 11 | 22.9 | NS (NS) |
| TnC | |||||
| All | 1–161 | 157 | 38 | 24.2 | 0.029 |
| N-lobe | 1–85 | 85 | 9 | 10.6 | <0.0001 |
| C-lobe | 86–161 | 72 | 29 | 40.3 | 0.036 (NS) |
Distribution is shown for all 563 troponin residues that were not implicated in recent summaries of clinical experience as sites of any pathogenic or possibly pathogenic (VUS) missense substitutions, but that did contain at least one missense substitution in the gnomAD v2, whole-exome, whole-genome population data. Areas unseen by cryo-EM are the same as in Table 1. P values for the observed densities were calculated as described in Materials and methods. NS indicates P > 0.05.