Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2998 | 9217;9218;9219 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| N2AB | 2998 | 9217;9218;9219 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| N2A | 2998 | 9217;9218;9219 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| N2B | 2952 | 9079;9080;9081 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| Novex-1 | 2952 | 9079;9080;9081 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| Novex-2 | 2952 | 9079;9080;9081 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
| Novex-3 | 2998 | 9217;9218;9219 | chr2:178768844;178768843;178768842 | chr2:179633571;179633570;179633569 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs374490159  |
-0.055 | None | N | 0.147 | 0.145 | None | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| S/T | rs374490159 |
-0.055 | None | N | 0.147 | 0.145 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/T | rs374490159 |
-0.055 | None | N | 0.147 | 0.145 | None | gnomAD-4.0.0 | 1.85877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69489E-06 | 1.09791E-05 | 0 |
| S/Y | None | None | 0.879 | D | 0.685 | 0.467 | 0.682911096811 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0803 | likely_benign | 0.0861 | benign | -0.251 | Destabilizing | 0.174 | N | 0.337 | neutral | D | 0.540556674 | None | None | N |
| S/C | 0.1647 | likely_benign | 0.1833 | benign | -0.548 | Destabilizing | 0.965 | D | 0.575 | neutral | N | 0.520099352 | None | None | N |
| S/D | 0.5288 | ambiguous | 0.5352 | ambiguous | 0.156 | Stabilizing | 0.575 | D | 0.391 | neutral | None | None | None | None | N |
| S/E | 0.6563 | likely_pathogenic | 0.6758 | pathogenic | 0.081 | Stabilizing | 0.575 | D | 0.382 | neutral | None | None | None | None | N |
| S/F | 0.3054 | likely_benign | 0.3232 | benign | -0.995 | Destabilizing | 0.879 | D | 0.685 | prob.neutral | D | 0.544097714 | None | None | N |
| S/G | 0.1297 | likely_benign | 0.1277 | benign | -0.316 | Destabilizing | 0.575 | D | 0.391 | neutral | None | None | None | None | N |
| S/H | 0.4562 | ambiguous | 0.4818 | ambiguous | -0.496 | Destabilizing | 0.991 | D | 0.579 | neutral | None | None | None | None | N |
| S/I | 0.2375 | likely_benign | 0.2459 | benign | -0.207 | Destabilizing | 0.704 | D | 0.602 | neutral | None | None | None | None | N |
| S/K | 0.7455 | likely_pathogenic | 0.7775 | pathogenic | -0.297 | Destabilizing | 0.575 | D | 0.391 | neutral | None | None | None | None | N |
| S/L | 0.1166 | likely_benign | 0.124 | benign | -0.207 | Destabilizing | 0.404 | N | 0.525 | neutral | None | None | None | None | N |
| S/M | 0.2358 | likely_benign | 0.2478 | benign | -0.434 | Destabilizing | 0.973 | D | 0.586 | neutral | None | None | None | None | N |
| S/N | 0.1736 | likely_benign | 0.1608 | benign | -0.226 | Destabilizing | 0.575 | D | 0.405 | neutral | None | None | None | None | N |
| S/P | 0.2013 | likely_benign | 0.1995 | benign | -0.197 | Destabilizing | 0.879 | D | 0.557 | neutral | N | 0.457034034 | None | None | N |
| S/Q | 0.5836 | likely_pathogenic | 0.6061 | pathogenic | -0.358 | Destabilizing | 0.906 | D | 0.507 | neutral | None | None | None | None | N |
| S/R | 0.6648 | likely_pathogenic | 0.7028 | pathogenic | -0.046 | Destabilizing | 0.826 | D | 0.561 | neutral | None | None | None | None | N |
| S/T | 0.0664 | likely_benign | 0.0633 | benign | -0.288 | Destabilizing | None | N | 0.147 | neutral | N | 0.439586615 | None | None | N |
| S/V | 0.2153 | likely_benign | 0.227 | benign | -0.197 | Destabilizing | 0.404 | N | 0.527 | neutral | None | None | None | None | N |
| S/W | 0.516 | ambiguous | 0.5552 | ambiguous | -1.106 | Destabilizing | 0.991 | D | 0.728 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2768 | likely_benign | 0.3145 | benign | -0.756 | Destabilizing | 0.879 | D | 0.685 | prob.neutral | D | 0.54392632 | 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.