Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24991 | 75196;75197;75198 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| N2AB | 23350 | 70273;70274;70275 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| N2A | 22423 | 67492;67493;67494 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| N2B | 15926 | 48001;48002;48003 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| Novex-1 | 16051 | 48376;48377;48378 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| Novex-2 | 16118 | 48577;48578;48579 | chr2:178571161;178571160;178571159 | chr2:179435888;179435887;179435886 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.001 | N | 0.199 | 0.058 | 0.308278614506 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs744427  |
-1.098 | 0.002 | N | 0.322 | 0.194 | None | gnomAD-2.1.1 | 4.79717E-03 | None | None | None | None | I | None | 5.08888E-02 | 2.00894E-03 | None | 0 | 0 | None | 2.61489E-04 | None | 0 | 1.48952E-04 | 1.68539E-03 |
| I/T | rs744427 |
-1.098 | 0.002 | N | 0.322 | 0.194 | None | gnomAD-3.1.2 | 1.42177E-02 | None | None | None | None | I | None | 4.97031E-02 | 4.45726E-03 | 0 | 0 | 1.93573E-04 | None | 9.43E-05 | 3.16456E-03 | 2.05894E-04 | 2.07297E-04 | 8.11843E-03 |
| I/T | rs744427 |
-1.098 | 0.002 | N | 0.322 | 0.194 | None | 1000 genomes | 1.63738E-02 | None | None | None | None | I | None | 5.82E-02 | 7.2E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs744427 |
-1.098 | 0.002 | N | 0.322 | 0.194 | None | gnomAD-4.0.0 | 2.78409E-03 | None | None | None | None | I | None | 5.20814E-02 | 2.51725E-03 | None | 0 | 2.23214E-05 | None | 1.56357E-05 | 1.98085E-03 | 1.5683E-04 | 1.9765E-04 | 3.4899E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1644 | likely_benign | 0.1672 | benign | -1.258 | Destabilizing | 0.25 | N | 0.538 | neutral | None | None | None | None | I |
| I/C | 0.511 | ambiguous | 0.5096 | ambiguous | -0.671 | Destabilizing | 0.977 | D | 0.6 | neutral | None | None | None | None | I |
| I/D | 0.7117 | likely_pathogenic | 0.7201 | pathogenic | -0.719 | Destabilizing | 0.85 | D | 0.637 | neutral | None | None | None | None | I |
| I/E | 0.5273 | ambiguous | 0.5371 | ambiguous | -0.792 | Destabilizing | 0.85 | D | 0.633 | neutral | None | None | None | None | I |
| I/F | 0.1732 | likely_benign | 0.174 | benign | -1.118 | Destabilizing | 0.81 | D | 0.583 | neutral | N | 0.517475937 | None | None | I |
| I/G | 0.5553 | ambiguous | 0.5496 | ambiguous | -1.491 | Destabilizing | 0.617 | D | 0.63 | neutral | None | None | None | None | I |
| I/H | 0.5355 | ambiguous | 0.5379 | ambiguous | -0.668 | Destabilizing | 0.992 | D | 0.641 | neutral | None | None | None | None | I |
| I/K | 0.3409 | ambiguous | 0.3554 | ambiguous | -0.661 | Destabilizing | 0.617 | D | 0.634 | neutral | None | None | None | None | I |
| I/L | 0.11 | likely_benign | 0.1118 | benign | -0.735 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.431049031 | None | None | I |
| I/M | 0.1026 | likely_benign | 0.0991 | benign | -0.46 | Destabilizing | 0.81 | D | 0.609 | neutral | N | 0.476072032 | None | None | I |
| I/N | 0.3182 | likely_benign | 0.3167 | benign | -0.361 | Destabilizing | 0.81 | D | 0.643 | neutral | N | 0.463741327 | None | None | I |
| I/P | 0.4295 | ambiguous | 0.4446 | ambiguous | -0.876 | Destabilizing | 0.92 | D | 0.645 | neutral | None | None | None | None | I |
| I/Q | 0.4154 | ambiguous | 0.4174 | ambiguous | -0.655 | Destabilizing | 0.92 | D | 0.64 | neutral | None | None | None | None | I |
| I/R | 0.267 | likely_benign | 0.2793 | benign | 0.015 | Stabilizing | 0.85 | D | 0.646 | neutral | None | None | None | None | I |
| I/S | 0.2405 | likely_benign | 0.2485 | benign | -0.899 | Destabilizing | 0.379 | N | 0.607 | neutral | N | 0.502410484 | None | None | I |
| I/T | 0.0899 | likely_benign | 0.082 | benign | -0.863 | Destabilizing | 0.002 | N | 0.322 | neutral | N | 0.468375268 | None | None | I |
| I/V | 0.0609 | likely_benign | 0.0604 | benign | -0.876 | Destabilizing | 0.002 | N | 0.216 | neutral | N | 0.450346868 | None | None | I |
| I/W | 0.7357 | likely_pathogenic | 0.7468 | pathogenic | -1.092 | Destabilizing | 0.992 | D | 0.654 | neutral | None | None | None | None | I |
| I/Y | 0.5354 | ambiguous | 0.5487 | ambiguous | -0.871 | Destabilizing | 0.92 | D | 0.617 | 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.