Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15839 | 47740;47741;47742 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| N2AB | 14198 | 42817;42818;42819 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| N2A | 13271 | 40036;40037;40038 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| N2B | 6774 | 20545;20546;20547 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| Novex-1 | 6899 | 20920;20921;20922 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| Novex-2 | 6966 | 21121;21122;21123 | chr2:178617836;178617835;178617834 | chr2:179482563;179482562;179482561 |
| 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/N | rs764388462  |
None | 0.602 | N | 0.579 | 0.252 | 0.69773716983 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs764388462 |
None | 0.602 | N | 0.579 | 0.252 | 0.69773716983 | gnomAD-4.0.0 | 6.58189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs764388462 |
-0.398 | 0.042 | N | 0.501 | 0.162 | None | gnomAD-2.1.1 | 1.18164E-04 | None | None | None | None | I | None | 0 | 0 | None | 2.7137E-03 | 0 | None | 0 | None | 0 | 2.35E-05 | 2.81452E-04 |
| I/T | rs764388462 |
-0.398 | 0.042 | N | 0.501 | 0.162 | None | gnomAD-3.1.2 | 5.27E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 2.30814E-03 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs764388462 |
-0.398 | 0.042 | N | 0.501 | 0.162 | None | gnomAD-4.0.0 | 6.20167E-05 | None | None | None | None | I | None | 0 | 0 | None | 2.30041E-03 | 6.70811E-05 | None | 0 | 0 | 1.78105E-05 | 1.09842E-05 | 1.12219E-04 |
| I/V | rs1553710021 |
None | None | N | 0.161 | 0.097 | 0.245101548738 | gnomAD-4.0.0 | 1.59405E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86343E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2565 | likely_benign | 0.2101 | benign | -0.674 | Destabilizing | None | N | 0.215 | neutral | None | None | None | None | I |
| I/C | 0.7163 | likely_pathogenic | 0.6638 | pathogenic | -0.722 | Destabilizing | 0.667 | D | 0.509 | neutral | None | None | None | None | I |
| I/D | 0.8907 | likely_pathogenic | 0.8841 | pathogenic | -0.303 | Destabilizing | 0.364 | N | 0.565 | neutral | None | None | None | None | I |
| I/E | 0.7733 | likely_pathogenic | 0.7697 | pathogenic | -0.396 | Destabilizing | 0.22 | N | 0.565 | neutral | None | None | None | None | I |
| I/F | 0.2414 | likely_benign | 0.257 | benign | -0.666 | Destabilizing | 0.175 | N | 0.397 | neutral | N | 0.468361956 | None | None | I |
| I/G | 0.7652 | likely_pathogenic | 0.72 | pathogenic | -0.83 | Destabilizing | 0.055 | N | 0.595 | neutral | None | None | None | None | I |
| I/H | 0.7152 | likely_pathogenic | 0.7014 | pathogenic | -0.042 | Destabilizing | 0.958 | D | 0.554 | neutral | None | None | None | None | I |
| I/K | 0.7171 | likely_pathogenic | 0.7041 | pathogenic | -0.424 | Destabilizing | 0.22 | N | 0.561 | neutral | None | None | None | None | I |
| I/L | 0.183 | likely_benign | 0.171 | benign | -0.388 | Destabilizing | 0.008 | N | 0.309 | neutral | N | 0.470255201 | None | None | I |
| I/M | 0.1401 | likely_benign | 0.1378 | benign | -0.474 | Destabilizing | 0.427 | N | 0.397 | neutral | N | 0.505901235 | None | None | I |
| I/N | 0.4685 | ambiguous | 0.4516 | ambiguous | -0.272 | Destabilizing | 0.602 | D | 0.579 | neutral | N | 0.478834278 | None | None | I |
| I/P | 0.8873 | likely_pathogenic | 0.8876 | pathogenic | -0.45 | Destabilizing | 0.364 | N | 0.576 | neutral | None | None | None | None | I |
| I/Q | 0.6585 | likely_pathogenic | 0.6311 | pathogenic | -0.507 | Destabilizing | 0.667 | D | 0.582 | neutral | None | None | None | None | I |
| I/R | 0.5761 | likely_pathogenic | 0.5712 | pathogenic | 0.175 | Stabilizing | 0.667 | D | 0.583 | neutral | None | None | None | None | I |
| I/S | 0.3775 | ambiguous | 0.3362 | benign | -0.708 | Destabilizing | 0.042 | N | 0.57 | neutral | N | 0.479929394 | None | None | I |
| I/T | 0.2282 | likely_benign | 0.2007 | benign | -0.694 | Destabilizing | 0.042 | N | 0.501 | neutral | N | 0.477085038 | None | None | I |
| I/V | 0.0813 | likely_benign | 0.0787 | benign | -0.45 | Destabilizing | None | N | 0.161 | neutral | N | 0.442504655 | None | None | I |
| I/W | 0.8106 | likely_pathogenic | 0.8475 | pathogenic | -0.664 | Destabilizing | 0.958 | D | 0.561 | neutral | None | None | None | None | I |
| I/Y | 0.6328 | likely_pathogenic | 0.6383 | pathogenic | -0.428 | Destabilizing | 0.667 | D | 0.503 | 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.