Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35460 | 106603;106604;106605 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| N2AB | 33819 | 101680;101681;101682 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| N2A | 32892 | 98899;98900;98901 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| N2B | 26395 | 79408;79409;79410 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| Novex-1 | 26520 | 79783;79784;79785 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| Novex-2 | 26587 | 79984;79985;79986 | chr2:178530113;178530112;178530111 | chr2:179394840;179394839;179394838 |
| 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 | rs1398739704  |
-2.203 | 0.025 | N | 0.401 | 0.469 | 0.669000193909 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/T | rs1398739704 |
-2.203 | 0.025 | N | 0.401 | 0.469 | 0.669000193909 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs1398739704 |
-2.203 | 0.025 | N | 0.401 | 0.469 | 0.669000193909 | gnomAD-4.0.0 | 5.63877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.80472E-06 | 0 | 1.61828E-05 |
| I/V | rs1688408023 |
None | None | N | 0.11 | 0.096 | 0.435479573448 | gnomAD-4.0.0 | 1.67422E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.92927E-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 | 0.658 | likely_pathogenic | 0.5742 | pathogenic | -2.216 | Highly Destabilizing | 0.014 | N | 0.359 | neutral | None | None | None | None | N |
| I/C | 0.9066 | likely_pathogenic | 0.8637 | pathogenic | -1.513 | Destabilizing | 0.326 | N | 0.477 | neutral | None | None | None | None | N |
| I/D | 0.9653 | likely_pathogenic | 0.9483 | pathogenic | -2.012 | Highly Destabilizing | 0.326 | N | 0.548 | neutral | None | None | None | None | N |
| I/E | 0.9206 | likely_pathogenic | 0.8844 | pathogenic | -1.8 | Destabilizing | 0.326 | N | 0.54 | neutral | None | None | None | None | N |
| I/F | 0.3234 | likely_benign | 0.2875 | benign | -1.331 | Destabilizing | 0.025 | N | 0.431 | neutral | D | 0.522653336 | None | None | N |
| I/G | 0.9264 | likely_pathogenic | 0.885 | pathogenic | -2.729 | Highly Destabilizing | 0.121 | N | 0.53 | neutral | None | None | None | None | N |
| I/H | 0.9229 | likely_pathogenic | 0.8949 | pathogenic | -2.01 | Highly Destabilizing | 0.848 | D | 0.55 | neutral | None | None | None | None | N |
| I/K | 0.8577 | likely_pathogenic | 0.8098 | pathogenic | -1.593 | Destabilizing | 0.326 | N | 0.533 | neutral | None | None | None | None | N |
| I/L | 0.1109 | likely_benign | 0.1088 | benign | -0.753 | Destabilizing | None | N | 0.102 | neutral | N | 0.431158967 | None | None | N |
| I/M | 0.1658 | likely_benign | 0.1511 | benign | -0.724 | Destabilizing | 0.153 | N | 0.478 | neutral | D | 0.523557413 | None | None | N |
| I/N | 0.7894 | likely_pathogenic | 0.7166 | pathogenic | -1.867 | Destabilizing | 0.527 | D | 0.564 | neutral | D | 0.523060744 | None | None | N |
| I/P | 0.9307 | likely_pathogenic | 0.9038 | pathogenic | -1.22 | Destabilizing | 0.326 | N | 0.553 | neutral | None | None | None | None | N |
| I/Q | 0.8772 | likely_pathogenic | 0.8314 | pathogenic | -1.722 | Destabilizing | 0.596 | D | 0.578 | neutral | None | None | None | None | N |
| I/R | 0.8031 | likely_pathogenic | 0.7466 | pathogenic | -1.394 | Destabilizing | 0.326 | N | 0.555 | neutral | None | None | None | None | N |
| I/S | 0.7884 | likely_pathogenic | 0.7157 | pathogenic | -2.598 | Highly Destabilizing | 0.049 | N | 0.469 | neutral | N | 0.5159704 | None | None | N |
| I/T | 0.711 | likely_pathogenic | 0.614 | pathogenic | -2.224 | Highly Destabilizing | 0.025 | N | 0.401 | neutral | N | 0.508409075 | None | None | N |
| I/V | 0.0885 | likely_benign | 0.0775 | benign | -1.22 | Destabilizing | None | N | 0.11 | neutral | N | 0.468066703 | None | None | N |
| I/W | 0.9334 | likely_pathogenic | 0.9182 | pathogenic | -1.568 | Destabilizing | 0.848 | D | 0.571 | neutral | None | None | None | None | N |
| I/Y | 0.8069 | likely_pathogenic | 0.7589 | pathogenic | -1.28 | Destabilizing | 0.326 | N | 0.491 | 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.