Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35484 | 106675;106676;106677 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| N2AB | 33843 | 101752;101753;101754 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| N2A | 32916 | 98971;98972;98973 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| N2B | 26419 | 79480;79481;79482 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| Novex-1 | 26544 | 79855;79856;79857 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| Novex-2 | 26611 | 80056;80057;80058 | chr2:178530041;178530040;178530039 | chr2:179394768;179394767;179394766 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs754163825  |
None | None | N | 0.126 | 0.073 | 0.110078149338 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs754163825 |
None | None | N | 0.126 | 0.073 | 0.110078149338 | gnomAD-4.0.0 | 6.57134E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 0 | 0 |
| T/N | None | None | 0.022 | N | 0.205 | 0.061 | 0.12205267543 | gnomAD-4.0.0 | 5.4854E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30035E-06 | 0 | 1.65937E-05 |
| T/P | None | None | 0.044 | N | 0.293 | 0.104 | 0.0401082797425 | gnomAD-4.0.0 | 1.59899E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86366E-06 | 0 | 0 |
| T/S | rs754163825 |
0.213 | 0.005 | N | 0.178 | 0.037 | 0.0401082797425 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| T/S | rs754163825 |
0.213 | 0.005 | N | 0.178 | 0.037 | 0.0401082797425 | gnomAD-4.0.0 | 3.42838E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.50025E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0756 | likely_benign | 0.0721 | benign | -0.481 | Destabilizing | None | N | 0.071 | neutral | N | 0.340613454 | None | None | N |
| T/C | 0.5283 | ambiguous | 0.5015 | ambiguous | -0.128 | Destabilizing | 0.177 | N | 0.224 | neutral | None | None | None | None | N |
| T/D | 0.2522 | likely_benign | 0.2375 | benign | 0.191 | Stabilizing | 0.029 | N | 0.263 | neutral | None | None | None | None | N |
| T/E | 0.2347 | likely_benign | 0.2203 | benign | 0.095 | Stabilizing | 0.029 | N | 0.29 | neutral | None | None | None | None | N |
| T/F | 0.1952 | likely_benign | 0.1709 | benign | -1.14 | Destabilizing | 0.029 | N | 0.314 | neutral | None | None | None | None | N |
| T/G | 0.2026 | likely_benign | 0.1943 | benign | -0.554 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| T/H | 0.2596 | likely_benign | 0.2273 | benign | -0.986 | Destabilizing | 0.396 | N | 0.244 | neutral | None | None | None | None | N |
| T/I | 0.1086 | likely_benign | 0.1001 | benign | -0.405 | Destabilizing | None | N | 0.126 | neutral | N | 0.401104553 | None | None | N |
| T/K | 0.1661 | likely_benign | 0.1533 | benign | -0.187 | Destabilizing | 0.029 | N | 0.295 | neutral | None | None | None | None | N |
| T/L | 0.1014 | likely_benign | 0.0905 | benign | -0.405 | Destabilizing | None | N | 0.097 | neutral | None | None | None | None | N |
| T/M | 0.1107 | likely_benign | 0.1018 | benign | 0.016 | Stabilizing | 0.096 | N | 0.223 | neutral | None | None | None | None | N |
| T/N | 0.1055 | likely_benign | 0.1008 | benign | 0.081 | Stabilizing | 0.022 | N | 0.205 | neutral | N | 0.436814637 | None | None | N |
| T/P | 0.1262 | likely_benign | 0.1063 | benign | -0.406 | Destabilizing | 0.044 | N | 0.293 | neutral | N | 0.365047752 | None | None | N |
| T/Q | 0.2217 | likely_benign | 0.2023 | benign | -0.22 | Destabilizing | 0.177 | N | 0.288 | neutral | None | None | None | None | N |
| T/R | 0.1514 | likely_benign | 0.1356 | benign | 0.034 | Stabilizing | 0.029 | N | 0.312 | neutral | None | None | None | None | N |
| T/S | 0.1049 | likely_benign | 0.1006 | benign | -0.135 | Destabilizing | 0.005 | N | 0.178 | neutral | N | 0.375515462 | None | None | N |
| T/V | 0.1109 | likely_benign | 0.1044 | benign | -0.406 | Destabilizing | None | N | 0.07 | neutral | None | None | None | None | N |
| T/W | 0.5764 | likely_pathogenic | 0.5343 | ambiguous | -1.121 | Destabilizing | 0.712 | D | 0.255 | neutral | None | None | None | None | N |
| T/Y | 0.2481 | likely_benign | 0.2166 | benign | -0.831 | Destabilizing | 0.177 | N | 0.326 | 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.