Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19537 | 58834;58835;58836 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| N2AB | 17896 | 53911;53912;53913 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| N2A | 16969 | 51130;51131;51132 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| N2B | 10472 | 31639;31640;31641 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| Novex-1 | 10597 | 32014;32015;32016 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| Novex-2 | 10664 | 32215;32216;32217 | chr2:178593691;178593690;178593689 | chr2:179458418;179458417;179458416 |
| 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/R | None | None | 0.667 | N | 0.628 | 0.472 | 0.568036332872 | gnomAD-4.0.0 | 6.84382E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99583E-07 | 0 | 0 |
| T/S | rs750320421  |
-0.949 | 0.22 | N | 0.435 | 0.193 | 0.141422826196 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/S | rs750320421 |
-0.949 | 0.22 | N | 0.435 | 0.193 | 0.141422826196 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/S | rs750320421 |
-0.949 | 0.22 | N | 0.435 | 0.193 | 0.141422826196 | gnomAD-4.0.0 | 5.12726E-06 | None | None | None | None | N | None | 3.38467E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78792E-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 | 0.1389 | likely_benign | 0.1227 | benign | -0.832 | Destabilizing | 0.055 | N | 0.453 | neutral | N | 0.495553107 | None | None | N |
| T/C | 0.4046 | ambiguous | 0.4006 | ambiguous | -0.33 | Destabilizing | 0.968 | D | 0.649 | neutral | None | None | None | None | N |
| T/D | 0.6311 | likely_pathogenic | 0.5806 | pathogenic | -0.149 | Destabilizing | 0.567 | D | 0.583 | neutral | None | None | None | None | N |
| T/E | 0.4293 | ambiguous | 0.4134 | ambiguous | -0.014 | Destabilizing | 0.567 | D | 0.58 | neutral | None | None | None | None | N |
| T/F | 0.5793 | likely_pathogenic | 0.5213 | ambiguous | -0.79 | Destabilizing | 0.567 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/G | 0.4059 | ambiguous | 0.3793 | ambiguous | -1.189 | Destabilizing | 0.567 | D | 0.631 | neutral | None | None | None | None | N |
| T/H | 0.5002 | ambiguous | 0.4373 | ambiguous | -1.267 | Destabilizing | 0.968 | D | 0.708 | prob.delet. | None | None | None | None | N |
| T/I | 0.3874 | ambiguous | 0.3831 | ambiguous | 0.069 | Stabilizing | 0.331 | N | 0.581 | neutral | N | 0.498288585 | None | None | N |
| T/K | 0.3667 | ambiguous | 0.3507 | ambiguous | -0.078 | Destabilizing | 0.497 | N | 0.58 | neutral | N | 0.481056476 | None | None | N |
| T/L | 0.1083 | likely_benign | 0.0996 | benign | 0.069 | Stabilizing | 0.001 | N | 0.397 | neutral | None | None | None | None | N |
| T/M | 0.0953 | likely_benign | 0.0919 | benign | 0.029 | Stabilizing | 0.832 | D | 0.657 | neutral | None | None | None | None | N |
| T/N | 0.1525 | likely_benign | 0.1309 | benign | -0.517 | Destabilizing | 0.726 | D | 0.531 | neutral | None | None | None | None | N |
| T/P | 0.1231 | likely_benign | 0.0918 | benign | -0.199 | Destabilizing | 0.001 | N | 0.42 | neutral | N | 0.473409927 | None | None | N |
| T/Q | 0.3188 | likely_benign | 0.2966 | benign | -0.378 | Destabilizing | 0.726 | D | 0.649 | neutral | None | None | None | None | N |
| T/R | 0.3016 | likely_benign | 0.2786 | benign | -0.189 | Destabilizing | 0.667 | D | 0.628 | neutral | N | 0.481879397 | None | None | N |
| T/S | 0.2314 | likely_benign | 0.204 | benign | -0.859 | Destabilizing | 0.22 | N | 0.435 | neutral | N | 0.48951272 | None | None | N |
| T/V | 0.2461 | likely_benign | 0.2526 | benign | -0.199 | Destabilizing | 0.157 | N | 0.437 | neutral | None | None | None | None | N |
| T/W | 0.8612 | likely_pathogenic | 0.8267 | pathogenic | -0.856 | Destabilizing | 0.968 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/Y | 0.5096 | ambiguous | 0.4503 | ambiguous | -0.476 | Destabilizing | 0.89 | D | 0.712 | prob.delet. | 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.