Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18179 | 54760;54761;54762 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| N2AB | 16538 | 49837;49838;49839 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| N2A | 15611 | 47056;47057;47058 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| N2B | 9114 | 27565;27566;27567 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| Novex-1 | 9239 | 27940;27941;27942 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| Novex-2 | 9306 | 28141;28142;28143 | chr2:178604152;178604151;178604150 | chr2:179468879;179468878;179468877 |
| 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/A | None | None | 0.201 | D | 0.354 | 0.147 | 0.227260227426 | gnomAD-4.0.0 | 2.05441E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70014E-06 | 0 | 0 |
| T/I | rs765149899  |
-0.141 | 0.004 | N | 0.214 | 0.317 | 0.311691414656 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/I | rs765149899 |
-0.141 | 0.004 | N | 0.214 | 0.317 | 0.311691414656 | gnomAD-4.0.0 | 1.59458E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86431E-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 | 0.216 | likely_benign | 0.1562 | benign | -0.748 | Destabilizing | 0.201 | N | 0.354 | neutral | D | 0.52431427 | None | None | N |
| T/C | 0.5878 | likely_pathogenic | 0.4932 | ambiguous | -0.442 | Destabilizing | 0.012 | N | 0.267 | neutral | None | None | None | None | N |
| T/D | 0.4332 | ambiguous | 0.3781 | ambiguous | -0.708 | Destabilizing | 0.617 | D | 0.408 | neutral | None | None | None | None | N |
| T/E | 0.4551 | ambiguous | 0.414 | ambiguous | -0.732 | Destabilizing | 0.617 | D | 0.409 | neutral | None | None | None | None | N |
| T/F | 0.6484 | likely_pathogenic | 0.5136 | ambiguous | -1.036 | Destabilizing | 0.85 | D | 0.435 | neutral | None | None | None | None | N |
| T/G | 0.1836 | likely_benign | 0.1489 | benign | -0.967 | Destabilizing | 0.447 | N | 0.405 | neutral | None | None | None | None | N |
| T/H | 0.442 | ambiguous | 0.3588 | ambiguous | -1.361 | Destabilizing | 0.992 | D | 0.389 | neutral | None | None | None | None | N |
| T/I | 0.7696 | likely_pathogenic | 0.6886 | pathogenic | -0.262 | Destabilizing | 0.004 | N | 0.214 | neutral | N | 0.496962367 | None | None | N |
| T/K | 0.4087 | ambiguous | 0.3849 | ambiguous | -0.719 | Destabilizing | 0.617 | D | 0.41 | neutral | None | None | None | None | N |
| T/L | 0.39 | ambiguous | 0.2701 | benign | -0.262 | Destabilizing | 0.103 | N | 0.387 | neutral | None | None | None | None | N |
| T/M | 0.2946 | likely_benign | 0.2117 | benign | 0.252 | Stabilizing | 0.85 | D | 0.387 | neutral | None | None | None | None | N |
| T/N | 0.1304 | likely_benign | 0.1072 | benign | -0.687 | Destabilizing | 0.549 | D | 0.386 | neutral | N | 0.510459538 | None | None | N |
| T/P | 0.6738 | likely_pathogenic | 0.5804 | pathogenic | -0.393 | Destabilizing | 0.896 | D | 0.395 | neutral | N | 0.501735307 | None | None | N |
| T/Q | 0.332 | likely_benign | 0.2784 | benign | -0.974 | Destabilizing | 0.92 | D | 0.394 | neutral | None | None | None | None | N |
| T/R | 0.3982 | ambiguous | 0.3471 | ambiguous | -0.399 | Destabilizing | 0.85 | D | 0.413 | neutral | None | None | None | None | N |
| T/S | 0.1068 | likely_benign | 0.0873 | benign | -0.877 | Destabilizing | 0.007 | N | 0.071 | neutral | N | 0.444407905 | None | None | N |
| T/V | 0.5515 | ambiguous | 0.4715 | ambiguous | -0.393 | Destabilizing | 0.103 | N | 0.327 | neutral | None | None | None | None | N |
| T/W | 0.8707 | likely_pathogenic | 0.8127 | pathogenic | -0.982 | Destabilizing | 0.992 | D | 0.457 | neutral | None | None | None | None | N |
| T/Y | 0.6154 | likely_pathogenic | 0.5176 | ambiguous | -0.719 | Destabilizing | 0.92 | D | 0.421 | 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.