Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26023 | 78292;78293;78294 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| N2AB | 24382 | 73369;73370;73371 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| N2A | 23455 | 70588;70589;70590 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| N2B | 16958 | 51097;51098;51099 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| Novex-1 | 17083 | 51472;51473;51474 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| Novex-2 | 17150 | 51673;51674;51675 | chr2:178568065;178568064;178568063 | chr2:179432792;179432791;179432790 |
| 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 | rs572384303  |
-0.882 | 0.001 | N | 0.178 | 0.24 | 0.418221603839 | gnomAD-2.1.1 | 5.24659E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 4.21651E-03 | None | 0 | 0 | 1.66778E-04 |
| I/T | rs572384303 |
-0.882 | 0.001 | N | 0.178 | 0.24 | 0.418221603839 | gnomAD-3.1.2 | 1.38092E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.34603E-03 | 0 |
| I/T | rs572384303 |
-0.882 | 0.001 | N | 0.178 | 0.24 | 0.418221603839 | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 7.2E-03 | None |
| I/T | rs572384303 |
-0.882 | 0.001 | N | 0.178 | 0.24 | 0.418221603839 | gnomAD-4.0.0 | 2.36772E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47771E-06 | 3.95292E-03 | 1.92197E-04 |
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 | 0.2111 | likely_benign | 0.1878 | benign | -1.579 | Destabilizing | 0.129 | N | 0.371 | neutral | None | None | None | None | I |
| I/C | 0.6807 | likely_pathogenic | 0.6234 | pathogenic | -0.763 | Destabilizing | 0.94 | D | 0.349 | neutral | None | None | None | None | I |
| I/D | 0.8206 | likely_pathogenic | 0.7921 | pathogenic | -1.177 | Destabilizing | 0.716 | D | 0.4 | neutral | None | None | None | None | I |
| I/E | 0.6668 | likely_pathogenic | 0.6304 | pathogenic | -1.213 | Destabilizing | 0.418 | N | 0.381 | neutral | None | None | None | None | I |
| I/F | 0.1412 | likely_benign | 0.1298 | benign | -1.21 | Destabilizing | 0.264 | N | 0.293 | neutral | None | None | None | None | I |
| I/G | 0.6499 | likely_pathogenic | 0.5942 | pathogenic | -1.859 | Destabilizing | 0.418 | N | 0.395 | neutral | None | None | None | None | I |
| I/H | 0.5542 | ambiguous | 0.485 | ambiguous | -1.011 | Destabilizing | 0.983 | D | 0.317 | neutral | None | None | None | None | I |
| I/K | 0.3919 | ambiguous | 0.3574 | ambiguous | -1.087 | Destabilizing | 0.351 | N | 0.401 | neutral | N | 0.500874476 | None | None | I |
| I/L | 0.069 | likely_benign | 0.0666 | benign | -0.9 | Destabilizing | None | N | 0.071 | neutral | N | 0.424491205 | None | None | I |
| I/M | 0.0862 | likely_benign | 0.0809 | benign | -0.563 | Destabilizing | 0.655 | D | 0.353 | neutral | N | 0.485193852 | None | None | I |
| I/N | 0.3718 | ambiguous | 0.3243 | benign | -0.823 | Destabilizing | 0.716 | D | 0.388 | neutral | None | None | None | None | I |
| I/P | 0.898 | likely_pathogenic | 0.8727 | pathogenic | -1.095 | Destabilizing | 0.836 | D | 0.387 | neutral | None | None | None | None | I |
| I/Q | 0.4626 | ambiguous | 0.4149 | ambiguous | -1.073 | Destabilizing | 0.836 | D | 0.356 | neutral | None | None | None | None | I |
| I/R | 0.2863 | likely_benign | 0.2589 | benign | -0.365 | Destabilizing | 0.655 | D | 0.391 | neutral | N | 0.497988886 | None | None | I |
| I/S | 0.2723 | likely_benign | 0.2307 | benign | -1.352 | Destabilizing | 0.264 | N | 0.343 | neutral | None | None | None | None | I |
| I/T | 0.0742 | likely_benign | 0.0688 | benign | -1.284 | Destabilizing | 0.001 | N | 0.178 | neutral | N | 0.413156704 | None | None | I |
| I/V | 0.0777 | likely_benign | 0.0737 | benign | -1.095 | Destabilizing | 0.021 | N | 0.195 | neutral | N | 0.508877884 | None | None | I |
| I/W | 0.725 | likely_pathogenic | 0.6917 | pathogenic | -1.249 | Destabilizing | 0.983 | D | 0.331 | neutral | None | None | None | None | I |
| I/Y | 0.5633 | ambiguous | 0.5291 | ambiguous | -1.058 | Destabilizing | 0.836 | D | 0.405 | 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.