Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28396 | 85411;85412;85413 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| N2AB | 26755 | 80488;80489;80490 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| N2A | 25828 | 77707;77708;77709 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| N2B | 19331 | 58216;58217;58218 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| Novex-1 | 19456 | 58591;58592;58593 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| Novex-2 | 19523 | 58792;58793;58794 | chr2:178560946;178560945;178560944 | chr2:179425673;179425672;179425671 |
| 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/T | rs371320129  |
-0.281 | None | N | 0.129 | 0.116 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/T | rs371320129 |
-0.281 | None | N | 0.129 | 0.116 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs371320129 |
-0.281 | None | N | 0.129 | 0.116 | None | gnomAD-4.0.0 | 1.85915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54279E-06 | 0 | 0 |
| I/V | rs1703421976 |
None | None | N | 0.119 | 0.143 | 0.288727942641 | gnomAD-4.0.0 | 1.59128E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-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 | 0.1229 | likely_benign | 0.1218 | benign | -0.527 | Destabilizing | 0.002 | N | 0.252 | neutral | None | None | None | None | N |
| I/C | 0.351 | ambiguous | 0.3459 | ambiguous | -0.665 | Destabilizing | 0.245 | N | 0.271 | neutral | None | None | None | None | N |
| I/D | 0.2692 | likely_benign | 0.2538 | benign | -0.23 | Destabilizing | 0.018 | N | 0.377 | neutral | None | None | None | None | N |
| I/E | 0.1595 | likely_benign | 0.1599 | benign | -0.329 | Destabilizing | 0.004 | N | 0.357 | neutral | None | None | None | None | N |
| I/F | 0.1201 | likely_benign | 0.1155 | benign | -0.621 | Destabilizing | 0.044 | N | 0.21 | neutral | None | None | None | None | N |
| I/G | 0.3039 | likely_benign | 0.283 | benign | -0.662 | Destabilizing | 0.018 | N | 0.329 | neutral | None | None | None | None | N |
| I/H | 0.1707 | likely_benign | 0.1627 | benign | -0.002 | Destabilizing | 0.245 | N | 0.395 | neutral | None | None | None | None | N |
| I/K | 0.0742 | likely_benign | 0.0751 | benign | -0.345 | Destabilizing | None | N | 0.181 | neutral | N | 0.354893126 | None | None | N |
| I/L | 0.0898 | likely_benign | 0.0888 | benign | -0.3 | Destabilizing | 0.001 | N | 0.183 | neutral | N | 0.4564442 | None | None | N |
| I/M | 0.0688 | likely_benign | 0.067 | benign | -0.431 | Destabilizing | 0.108 | N | 0.243 | neutral | N | 0.465583758 | None | None | N |
| I/N | 0.09 | likely_benign | 0.0857 | benign | -0.17 | Destabilizing | 0.018 | N | 0.366 | neutral | None | None | None | None | N |
| I/P | 0.7411 | likely_pathogenic | 0.706 | pathogenic | -0.344 | Destabilizing | 0.037 | N | 0.423 | neutral | None | None | None | None | N |
| I/Q | 0.1106 | likely_benign | 0.1089 | benign | -0.389 | Destabilizing | 0.009 | N | 0.421 | neutral | None | None | None | None | N |
| I/R | 0.0645 | likely_benign | 0.0673 | benign | 0.191 | Stabilizing | 0.007 | N | 0.333 | neutral | N | 0.382754518 | None | None | N |
| I/S | 0.1075 | likely_benign | 0.1064 | benign | -0.575 | Destabilizing | 0.004 | N | 0.269 | neutral | None | None | None | None | N |
| I/T | 0.0774 | likely_benign | 0.0807 | benign | -0.569 | Destabilizing | None | N | 0.129 | neutral | N | 0.467871915 | None | None | N |
| I/V | 0.0643 | likely_benign | 0.0656 | benign | -0.344 | Destabilizing | None | N | 0.119 | neutral | N | 0.394587665 | None | None | N |
| I/W | 0.5081 | ambiguous | 0.4791 | ambiguous | -0.645 | Destabilizing | 0.788 | D | 0.375 | neutral | None | None | None | None | N |
| I/Y | 0.2497 | likely_benign | 0.2442 | benign | -0.395 | Destabilizing | 0.085 | N | 0.381 | 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.