Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24804 | 74635;74636;74637 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| N2AB | 23163 | 69712;69713;69714 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| N2A | 22236 | 66931;66932;66933 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| N2B | 15739 | 47440;47441;47442 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| Novex-1 | 15864 | 47815;47816;47817 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| Novex-2 | 15931 | 48016;48017;48018 | chr2:178571722;178571721;178571720 | chr2:179436449;179436448;179436447 |
| 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 | None | None | 0.549 | N | 0.345 | 0.267 | 0.723580609706 | gnomAD-4.0.0 | 1.36863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79917E-06 | 0 | 0 |
| I/V | rs544547448  |
-0.493 | 0.001 | N | 0.103 | 0.065 | 0.489658423131 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs544547448 |
-0.493 | 0.001 | N | 0.103 | 0.065 | 0.489658423131 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs544547448 |
-0.493 | 0.001 | N | 0.103 | 0.065 | 0.489658423131 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs544547448 |
-0.493 | 0.001 | N | 0.103 | 0.065 | 0.489658423131 | gnomAD-4.0.0 | 6.56935E-06 | None | None | None | None | N | None | 2.40547E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.3426 | ambiguous | 0.3405 | ambiguous | -1.443 | Destabilizing | 0.25 | N | 0.387 | neutral | None | None | None | None | N |
| I/C | 0.7627 | likely_pathogenic | 0.7592 | pathogenic | -0.848 | Destabilizing | 0.992 | D | 0.401 | neutral | None | None | None | None | N |
| I/D | 0.8373 | likely_pathogenic | 0.8311 | pathogenic | -0.678 | Destabilizing | 0.739 | D | 0.456 | neutral | None | None | None | None | N |
| I/E | 0.7031 | likely_pathogenic | 0.7069 | pathogenic | -0.69 | Destabilizing | 0.617 | D | 0.456 | neutral | None | None | None | None | N |
| I/F | 0.256 | likely_benign | 0.2485 | benign | -1.003 | Destabilizing | 0.81 | D | 0.381 | neutral | N | 0.520522168 | None | None | N |
| I/G | 0.8005 | likely_pathogenic | 0.8041 | pathogenic | -1.744 | Destabilizing | 0.447 | N | 0.464 | neutral | None | None | None | None | N |
| I/H | 0.6092 | likely_pathogenic | 0.5924 | pathogenic | -0.913 | Destabilizing | 0.977 | D | 0.477 | neutral | None | None | None | None | N |
| I/K | 0.5135 | ambiguous | 0.5174 | ambiguous | -0.885 | Destabilizing | 0.85 | D | 0.45 | neutral | None | None | None | None | N |
| I/L | 0.1605 | likely_benign | 0.1638 | benign | -0.705 | Destabilizing | 0.099 | N | 0.267 | neutral | D | 0.532307396 | None | None | N |
| I/M | 0.1261 | likely_benign | 0.1209 | benign | -0.55 | Destabilizing | 0.916 | D | 0.405 | neutral | N | 0.514027708 | None | None | N |
| I/N | 0.3807 | ambiguous | 0.3652 | ambiguous | -0.689 | Destabilizing | 0.004 | N | 0.389 | neutral | N | 0.50583287 | None | None | N |
| I/P | 0.9698 | likely_pathogenic | 0.9696 | pathogenic | -0.919 | Destabilizing | 0.972 | D | 0.505 | neutral | None | None | None | None | N |
| I/Q | 0.5396 | ambiguous | 0.5354 | ambiguous | -0.876 | Destabilizing | 0.85 | D | 0.506 | neutral | None | None | None | None | N |
| I/R | 0.403 | ambiguous | 0.4047 | ambiguous | -0.301 | Destabilizing | 0.85 | D | 0.512 | neutral | None | None | None | None | N |
| I/S | 0.3456 | ambiguous | 0.3316 | benign | -1.316 | Destabilizing | 0.379 | N | 0.414 | neutral | D | 0.527765581 | None | None | N |
| I/T | 0.1392 | likely_benign | 0.126 | benign | -1.214 | Destabilizing | 0.549 | D | 0.345 | neutral | N | 0.49907747 | None | None | N |
| I/V | 0.0638 | likely_benign | 0.0666 | benign | -0.919 | Destabilizing | 0.001 | N | 0.103 | neutral | N | 0.475472678 | None | None | N |
| I/W | 0.8989 | likely_pathogenic | 0.8873 | pathogenic | -1.045 | Destabilizing | 0.992 | D | 0.601 | neutral | None | None | None | None | N |
| I/Y | 0.6484 | likely_pathogenic | 0.6449 | pathogenic | -0.818 | Destabilizing | 0.92 | D | 0.437 | 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.