Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26988 | 81187;81188;81189 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| N2AB | 25347 | 76264;76265;76266 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| N2A | 24420 | 73483;73484;73485 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| N2B | 17923 | 53992;53993;53994 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| Novex-1 | 18048 | 54367;54368;54369 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| Novex-2 | 18115 | 54568;54569;54570 | chr2:178565170;178565169;178565168 | chr2:179429897;179429896;179429895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs755899399  |
-0.399 | 0.007 | N | 0.154 | 0.061 | 0.117506650769 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| D/E | rs755899399 |
-0.399 | 0.007 | N | 0.154 | 0.061 | 0.117506650769 | 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 |
| D/E | rs755899399 |
-0.399 | 0.007 | N | 0.154 | 0.061 | 0.117506650769 | gnomAD-4.0.0 | 6.84363E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87357E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2845 | likely_benign | 0.3017 | benign | -0.965 | Destabilizing | 0.684 | D | 0.322 | neutral | N | 0.486968279 | None | None | N |
| D/C | 0.7559 | likely_pathogenic | 0.7894 | pathogenic | -0.38 | Destabilizing | 0.996 | D | 0.437 | neutral | None | None | None | None | N |
| D/E | 0.193 | likely_benign | 0.2018 | benign | -0.633 | Destabilizing | 0.007 | N | 0.154 | neutral | N | 0.489756192 | None | None | N |
| D/F | 0.8352 | likely_pathogenic | 0.829 | pathogenic | -0.575 | Destabilizing | 0.984 | D | 0.407 | neutral | None | None | None | None | N |
| D/G | 0.2773 | likely_benign | 0.3023 | benign | -1.294 | Destabilizing | 0.521 | D | 0.338 | neutral | N | 0.472471648 | None | None | N |
| D/H | 0.4923 | ambiguous | 0.5336 | ambiguous | -0.772 | Destabilizing | 0.939 | D | 0.381 | neutral | N | 0.476434894 | None | None | N |
| D/I | 0.686 | likely_pathogenic | 0.68 | pathogenic | -0.09 | Destabilizing | 0.91 | D | 0.424 | neutral | None | None | None | None | N |
| D/K | 0.6627 | likely_pathogenic | 0.6951 | pathogenic | -0.406 | Destabilizing | 0.59 | D | 0.351 | neutral | None | None | None | None | N |
| D/L | 0.6454 | likely_pathogenic | 0.6401 | pathogenic | -0.09 | Destabilizing | 0.91 | D | 0.403 | neutral | None | None | None | None | N |
| D/M | 0.7744 | likely_pathogenic | 0.7714 | pathogenic | 0.398 | Stabilizing | 0.996 | D | 0.395 | neutral | None | None | None | None | N |
| D/N | 0.1041 | likely_benign | 0.1183 | benign | -0.824 | Destabilizing | 0.003 | N | 0.086 | neutral | N | 0.479056409 | None | None | N |
| D/P | 0.9266 | likely_pathogenic | 0.9329 | pathogenic | -0.359 | Destabilizing | 0.953 | D | 0.401 | neutral | None | None | None | None | N |
| D/Q | 0.5256 | ambiguous | 0.5495 | ambiguous | -0.741 | Destabilizing | 0.835 | D | 0.39 | neutral | None | None | None | None | N |
| D/R | 0.7037 | likely_pathogenic | 0.7309 | pathogenic | -0.225 | Destabilizing | 0.91 | D | 0.385 | neutral | None | None | None | None | N |
| D/S | 0.1458 | likely_benign | 0.1647 | benign | -1.122 | Destabilizing | 0.373 | N | 0.349 | neutral | None | None | None | None | N |
| D/T | 0.2704 | likely_benign | 0.297 | benign | -0.847 | Destabilizing | 0.037 | N | 0.261 | neutral | None | None | None | None | N |
| D/V | 0.4797 | ambiguous | 0.472 | ambiguous | -0.359 | Destabilizing | 0.884 | D | 0.404 | neutral | N | 0.505326023 | None | None | N |
| D/W | 0.9636 | likely_pathogenic | 0.9639 | pathogenic | -0.299 | Destabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | N |
| D/Y | 0.4542 | ambiguous | 0.4572 | ambiguous | -0.299 | Destabilizing | 0.979 | D | 0.408 | neutral | D | 0.523012205 | 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.