Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2798 | 8617;8618;8619 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| N2AB | 2798 | 8617;8618;8619 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| N2A | 2798 | 8617;8618;8619 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| N2B | 2752 | 8479;8480;8481 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| Novex-1 | 2752 | 8479;8480;8481 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| Novex-2 | 2752 | 8479;8480;8481 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
| Novex-3 | 2798 | 8617;8618;8619 | chr2:178770309;178770308;178770307 | chr2:179635036;179635035;179635034 |
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/L | None | None | 0.031 | N | 0.093 | 0.128 | 0.28722502521 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs751135365  |
-0.533 | 0.961 | N | 0.521 | 0.36 | 0.515938915144 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| I/T | rs751135365 |
-0.533 | 0.961 | N | 0.521 | 0.36 | 0.515938915144 | gnomAD-4.0.0 | 1.36813E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79857E-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 | 0.8965 | likely_pathogenic | 0.9068 | pathogenic | -0.633 | Destabilizing | 0.931 | D | 0.559 | neutral | None | None | None | None | I |
| I/C | 0.9619 | likely_pathogenic | 0.9711 | pathogenic | -0.766 | Destabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | I |
| I/D | 0.9896 | likely_pathogenic | 0.9907 | pathogenic | 0.189 | Stabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | I |
| I/E | 0.9518 | likely_pathogenic | 0.9548 | pathogenic | 0.13 | Stabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| I/F | 0.539 | ambiguous | 0.5532 | ambiguous | -0.419 | Destabilizing | 0.989 | D | 0.493 | neutral | N | 0.508440468 | None | None | I |
| I/G | 0.9758 | likely_pathogenic | 0.9791 | pathogenic | -0.822 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | I |
| I/H | 0.9371 | likely_pathogenic | 0.9521 | pathogenic | 0.005 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| I/K | 0.8968 | likely_pathogenic | 0.9216 | pathogenic | -0.355 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| I/L | 0.2463 | likely_benign | 0.2323 | benign | -0.246 | Destabilizing | 0.031 | N | 0.093 | neutral | N | 0.445085016 | None | None | I |
| I/M | 0.2544 | likely_benign | 0.2692 | benign | -0.411 | Destabilizing | 0.989 | D | 0.513 | neutral | N | 0.468782313 | None | None | I |
| I/N | 0.8544 | likely_pathogenic | 0.8775 | pathogenic | -0.292 | Destabilizing | 0.998 | D | 0.624 | neutral | N | 0.442190736 | None | None | I |
| I/P | 0.985 | likely_pathogenic | 0.9852 | pathogenic | -0.342 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | I |
| I/Q | 0.885 | likely_pathogenic | 0.907 | pathogenic | -0.437 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | I |
| I/R | 0.8594 | likely_pathogenic | 0.8912 | pathogenic | 0.133 | Stabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | I |
| I/S | 0.849 | likely_pathogenic | 0.8709 | pathogenic | -0.828 | Destabilizing | 0.994 | D | 0.521 | neutral | N | 0.456002174 | None | None | I |
| I/T | 0.6939 | likely_pathogenic | 0.7334 | pathogenic | -0.773 | Destabilizing | 0.961 | D | 0.521 | neutral | N | 0.432483097 | None | None | I |
| I/V | 0.1968 | likely_benign | 0.1928 | benign | -0.342 | Destabilizing | 0.122 | N | 0.117 | neutral | N | 0.431557156 | None | None | I |
| I/W | 0.9524 | likely_pathogenic | 0.9603 | pathogenic | -0.439 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/Y | 0.9047 | likely_pathogenic | 0.9219 | pathogenic | -0.205 | Destabilizing | 0.999 | D | 0.547 | 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.