Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1509 | 4750;4751;4752 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| N2AB | 1509 | 4750;4751;4752 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| N2A | 1509 | 4750;4751;4752 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| N2B | 1463 | 4612;4613;4614 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| Novex-1 | 1463 | 4612;4613;4614 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| Novex-2 | 1463 | 4612;4613;4614 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
| Novex-3 | 1509 | 4750;4751;4752 | chr2:178777540;178777539;178777538 | chr2:179642267;179642266;179642265 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | rs794729575  |
None | 0.999 | D | 0.575 | 0.634 | 0.543561272632 | gnomAD-4.0.0 | 1.36832E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79868E-06 | 0 | 0 |
| E/G | rs794729575 |
-0.086 | 1.0 | D | 0.569 | 0.67 | 0.567747928639 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| E/G | rs794729575 |
-0.086 | 1.0 | D | 0.569 | 0.67 | 0.567747928639 | gnomAD-4.0.0 | 7.52574E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89276E-06 | 0 | 0 |
| E/K | rs1270432206 |
0.698 | 0.999 | D | 0.605 | 0.593 | 0.521173705876 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/K | rs1270432206 |
0.698 | 0.999 | D | 0.605 | 0.593 | 0.521173705876 | gnomAD-4.0.0 | 6.8162E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32237E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.7413 | likely_pathogenic | 0.804 | pathogenic | -0.02 | Destabilizing | 0.999 | D | 0.575 | neutral | D | 0.530180025 | None | None | I |
| E/C | 0.9969 | likely_pathogenic | 0.9977 | pathogenic | -0.159 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| E/D | 0.4864 | ambiguous | 0.5655 | pathogenic | -0.299 | Destabilizing | 0.999 | D | 0.478 | neutral | N | 0.511526326 | None | None | I |
| E/F | 0.9966 | likely_pathogenic | 0.9974 | pathogenic | -0.116 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| E/G | 0.7128 | likely_pathogenic | 0.7722 | pathogenic | -0.121 | Destabilizing | 1.0 | D | 0.569 | neutral | D | 0.554564322 | None | None | I |
| E/H | 0.9798 | likely_pathogenic | 0.9857 | pathogenic | 0.491 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| E/I | 0.9765 | likely_pathogenic | 0.9818 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| E/K | 0.8492 | likely_pathogenic | 0.8855 | pathogenic | 0.389 | Stabilizing | 0.999 | D | 0.605 | neutral | D | 0.577874217 | None | None | I |
| E/L | 0.9737 | likely_pathogenic | 0.981 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| E/M | 0.9751 | likely_pathogenic | 0.9809 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| E/N | 0.9021 | likely_pathogenic | 0.9282 | pathogenic | 0.223 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| E/P | 0.9271 | likely_pathogenic | 0.9455 | pathogenic | 0.135 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| E/Q | 0.7641 | likely_pathogenic | 0.8251 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.591 | neutral | D | 0.56715011 | None | None | I |
| E/R | 0.9096 | likely_pathogenic | 0.9324 | pathogenic | 0.602 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| E/S | 0.8313 | likely_pathogenic | 0.8743 | pathogenic | 0.067 | Stabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | I |
| E/T | 0.9037 | likely_pathogenic | 0.927 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| E/V | 0.9264 | likely_pathogenic | 0.9451 | pathogenic | 0.135 | Stabilizing | 1.0 | D | 0.623 | neutral | D | 0.642530039 | None | None | I |
| E/W | 0.9981 | likely_pathogenic | 0.9986 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| E/Y | 0.9893 | likely_pathogenic | 0.9927 | pathogenic | 0.102 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
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.