Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16297 | 49114;49115;49116 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| N2AB | 14656 | 44191;44192;44193 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| N2A | 13729 | 41410;41411;41412 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| N2B | 7232 | 21919;21920;21921 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| Novex-1 | 7357 | 22294;22295;22296 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| Novex-2 | 7424 | 22495;22496;22497 | chr2:178614625;178614624;178614623 | chr2:179479352;179479351;179479350 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs754110019  |
0.217 | None | N | 0.243 | 0.136 | 0.294918367191 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 1.79E-05 | 0 |
| M/I | rs754110019 |
0.217 | None | N | 0.243 | 0.136 | 0.294918367191 | gnomAD-4.0.0 | 5.47771E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53318E-05 | None | 0 | 0 | 6.29925E-06 | 0 | 0 |
| M/R | rs1488829244 |
0.943 | 0.001 | N | 0.333 | 0.148 | 0.141422826196 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/R | rs1488829244 |
0.943 | 0.001 | N | 0.333 | 0.148 | 0.141422826196 | gnomAD-4.0.0 | 1.36942E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79978E-06 | 0 | 0 |
| M/T | None | None | None | N | 0.182 | 0.117 | 0.173771789658 | gnomAD-4.0.0 | 9.58597E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25984E-05 | 0 | 0 |
| M/V | None | None | None | N | 0.122 | 0.198 | 0.355242300401 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1967 | likely_benign | 0.1394 | benign | -0.49 | Destabilizing | None | N | 0.183 | neutral | None | None | None | None | N |
| M/C | 0.3477 | ambiguous | 0.3148 | benign | -0.52 | Destabilizing | 0.041 | N | 0.401 | neutral | None | None | None | None | N |
| M/D | 0.5941 | likely_pathogenic | 0.4402 | ambiguous | 0.385 | Stabilizing | 0.002 | N | 0.375 | neutral | None | None | None | None | N |
| M/E | 0.4288 | ambiguous | 0.2474 | benign | 0.343 | Stabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | N |
| M/F | 0.3457 | ambiguous | 0.2555 | benign | -0.066 | Destabilizing | 0.009 | N | 0.232 | neutral | None | None | None | None | N |
| M/G | 0.3456 | ambiguous | 0.2967 | benign | -0.68 | Destabilizing | 0.001 | N | 0.322 | neutral | None | None | None | None | N |
| M/H | 0.3036 | likely_benign | 0.2439 | benign | 0.165 | Stabilizing | None | N | 0.202 | neutral | None | None | None | None | N |
| M/I | 0.2262 | likely_benign | 0.1911 | benign | -0.08 | Destabilizing | None | N | 0.243 | neutral | N | 0.420909745 | None | None | N |
| M/K | 0.1467 | likely_benign | 0.1086 | benign | 0.375 | Stabilizing | None | N | 0.181 | neutral | N | 0.352151881 | None | None | N |
| M/L | 0.1535 | likely_benign | 0.1246 | benign | -0.08 | Destabilizing | None | N | 0.127 | neutral | N | 0.381352318 | None | None | N |
| M/N | 0.2115 | likely_benign | 0.1463 | benign | 0.482 | Stabilizing | 0.001 | N | 0.353 | neutral | None | None | None | None | N |
| M/P | 0.9696 | likely_pathogenic | 0.959 | pathogenic | -0.187 | Destabilizing | 0.008 | N | 0.363 | neutral | None | None | None | None | N |
| M/Q | 0.1816 | likely_benign | 0.1302 | benign | 0.344 | Stabilizing | None | N | 0.146 | neutral | None | None | None | None | N |
| M/R | 0.2036 | likely_benign | 0.1461 | benign | 0.856 | Stabilizing | 0.001 | N | 0.333 | neutral | N | 0.362315158 | None | None | N |
| M/S | 0.2195 | likely_benign | 0.1601 | benign | -0.005 | Destabilizing | None | N | 0.185 | neutral | None | None | None | None | N |
| M/T | 0.1589 | likely_benign | 0.1015 | benign | 0.06 | Stabilizing | None | N | 0.182 | neutral | N | 0.419211861 | None | None | N |
| M/V | 0.0981 | likely_benign | 0.0813 | benign | -0.187 | Destabilizing | None | N | 0.122 | neutral | N | 0.380162884 | None | None | N |
| M/W | 0.7254 | likely_pathogenic | 0.6009 | pathogenic | -0.052 | Destabilizing | 0.316 | N | 0.319 | neutral | None | None | None | None | N |
| M/Y | 0.4596 | ambiguous | 0.3738 | ambiguous | 0.089 | Stabilizing | 0.009 | N | 0.379 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.