Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24865 | 74818;74819;74820 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| N2AB | 23224 | 69895;69896;69897 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| N2A | 22297 | 67114;67115;67116 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| N2B | 15800 | 47623;47624;47625 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| Novex-1 | 15925 | 47998;47999;48000 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| Novex-2 | 15992 | 48199;48200;48201 | chr2:178571539;178571538;178571537 | chr2:179436266;179436265;179436264 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.773 | N | 0.481 | 0.238 | 0.230578612272 | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85959E-06 | 0 | 0 |
| R/S | rs1261180608  |
None | 0.099 | N | 0.343 | 0.198 | 0.154104182512 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1261180608 |
None | 0.099 | N | 0.343 | 0.198 | 0.154104182512 | gnomAD-4.0.0 | 2.56425E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.87116E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9722 | likely_pathogenic | 0.9696 | pathogenic | 0.029 | Stabilizing | 0.693 | D | 0.563 | neutral | None | None | None | None | N |
| R/C | 0.8304 | likely_pathogenic | 0.83 | pathogenic | -0.206 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| R/D | 0.9858 | likely_pathogenic | 0.9855 | pathogenic | -0.223 | Destabilizing | 0.975 | D | 0.575 | neutral | None | None | None | None | N |
| R/E | 0.9553 | likely_pathogenic | 0.9491 | pathogenic | -0.183 | Destabilizing | 0.916 | D | 0.511 | neutral | None | None | None | None | N |
| R/F | 0.985 | likely_pathogenic | 0.9833 | pathogenic | -0.279 | Destabilizing | 0.987 | D | 0.671 | neutral | None | None | None | None | N |
| R/G | 0.9103 | likely_pathogenic | 0.8984 | pathogenic | -0.113 | Destabilizing | 0.805 | D | 0.535 | neutral | N | 0.504858931 | None | None | N |
| R/H | 0.6835 | likely_pathogenic | 0.6574 | pathogenic | -0.571 | Destabilizing | 0.996 | D | 0.581 | neutral | None | None | None | None | N |
| R/I | 0.9752 | likely_pathogenic | 0.9735 | pathogenic | 0.359 | Stabilizing | 0.987 | D | 0.665 | neutral | None | None | None | None | N |
| R/K | 0.5725 | likely_pathogenic | 0.5446 | ambiguous | -0.114 | Destabilizing | 0.773 | D | 0.481 | neutral | N | 0.512187548 | None | None | N |
| R/L | 0.9317 | likely_pathogenic | 0.9317 | pathogenic | 0.359 | Stabilizing | 0.916 | D | 0.543 | neutral | None | None | None | None | N |
| R/M | 0.9594 | likely_pathogenic | 0.9572 | pathogenic | -0.044 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.508008595 | None | None | N |
| R/N | 0.9785 | likely_pathogenic | 0.9781 | pathogenic | 0.017 | Stabilizing | 0.916 | D | 0.563 | neutral | None | None | None | None | N |
| R/P | 0.9932 | likely_pathogenic | 0.9932 | pathogenic | 0.267 | Stabilizing | 0.987 | D | 0.667 | neutral | None | None | None | None | N |
| R/Q | 0.681 | likely_pathogenic | 0.6559 | pathogenic | -0.046 | Destabilizing | 0.975 | D | 0.572 | neutral | None | None | None | None | N |
| R/S | 0.9768 | likely_pathogenic | 0.9749 | pathogenic | -0.208 | Destabilizing | 0.099 | N | 0.343 | neutral | N | 0.49979704 | None | None | N |
| R/T | 0.9629 | likely_pathogenic | 0.9614 | pathogenic | -0.061 | Destabilizing | 0.805 | D | 0.598 | neutral | N | 0.483651365 | None | None | N |
| R/V | 0.9739 | likely_pathogenic | 0.9721 | pathogenic | 0.267 | Stabilizing | 0.975 | D | 0.663 | neutral | None | None | None | None | N |
| R/W | 0.8564 | likely_pathogenic | 0.8442 | pathogenic | -0.437 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | N | 0.519529484 | None | None | N |
| R/Y | 0.9499 | likely_pathogenic | 0.9481 | pathogenic | -0.03 | Destabilizing | 0.996 | D | 0.667 | 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.