Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3093 | 9502;9503;9504 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| N2AB | 3093 | 9502;9503;9504 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| N2A | 3093 | 9502;9503;9504 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| N2B | 3047 | 9364;9365;9366 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| Novex-1 | 3047 | 9364;9365;9366 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| Novex-2 | 3047 | 9364;9365;9366 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
| Novex-3 | 3093 | 9502;9503;9504 | chr2:178768042;178768041;178768040 | chr2:179632769;179632768;179632767 |
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/N | rs377376861  |
-0.251 | 0.007 | N | 0.212 | 0.153 | None | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.81E-06 | 0 |
| D/N | rs377376861 |
-0.251 | 0.007 | N | 0.212 | 0.153 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs377376861 |
-0.251 | 0.007 | N | 0.212 | 0.153 | None | gnomAD-4.0.0 | 3.09785E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54234E-06 | 2.19578E-05 | 0 |
| D/Y | None | None | 0.642 | N | 0.651 | 0.284 | 0.255270683199 | gnomAD-4.0.0 | 6.84078E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 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 | 0.6436 | likely_pathogenic | 0.6717 | pathogenic | -0.648 | Destabilizing | 0.505 | D | 0.558 | neutral | N | 0.447584456 | None | None | N |
| D/C | 0.9201 | likely_pathogenic | 0.9404 | pathogenic | -0.25 | Destabilizing | 0.991 | D | 0.673 | neutral | None | None | None | None | N |
| D/E | 0.5289 | ambiguous | 0.5731 | pathogenic | -0.57 | Destabilizing | 0.003 | N | 0.243 | neutral | N | 0.359885113 | None | None | N |
| D/F | 0.952 | likely_pathogenic | 0.9598 | pathogenic | -0.342 | Destabilizing | 0.826 | D | 0.645 | neutral | None | None | None | None | N |
| D/G | 0.2545 | likely_benign | 0.2696 | benign | -0.934 | Destabilizing | 0.338 | N | 0.524 | neutral | N | 0.331471501 | None | None | N |
| D/H | 0.8161 | likely_pathogenic | 0.841 | pathogenic | -0.477 | Destabilizing | 0.017 | N | 0.391 | neutral | N | 0.515702092 | None | None | N |
| D/I | 0.9575 | likely_pathogenic | 0.9604 | pathogenic | 0.087 | Stabilizing | 0.906 | D | 0.652 | neutral | None | None | None | None | N |
| D/K | 0.9099 | likely_pathogenic | 0.9169 | pathogenic | -0.279 | Destabilizing | 0.404 | N | 0.537 | neutral | None | None | None | None | N |
| D/L | 0.902 | likely_pathogenic | 0.9148 | pathogenic | 0.087 | Stabilizing | 0.826 | D | 0.633 | neutral | None | None | None | None | N |
| D/M | 0.9581 | likely_pathogenic | 0.9669 | pathogenic | 0.431 | Stabilizing | 0.991 | D | 0.649 | neutral | None | None | None | None | N |
| D/N | 0.1387 | likely_benign | 0.1565 | benign | -0.655 | Destabilizing | 0.007 | N | 0.212 | neutral | N | 0.347594097 | None | None | N |
| D/P | 0.9944 | likely_pathogenic | 0.9936 | pathogenic | -0.135 | Destabilizing | 0.906 | D | 0.554 | neutral | None | None | None | None | N |
| D/Q | 0.8576 | likely_pathogenic | 0.8757 | pathogenic | -0.569 | Destabilizing | 0.704 | D | 0.483 | neutral | None | None | None | None | N |
| D/R | 0.904 | likely_pathogenic | 0.908 | pathogenic | -0.057 | Destabilizing | 0.826 | D | 0.603 | neutral | None | None | None | None | N |
| D/S | 0.4035 | ambiguous | 0.4379 | ambiguous | -0.833 | Destabilizing | 0.404 | N | 0.446 | neutral | None | None | None | None | N |
| D/T | 0.8662 | likely_pathogenic | 0.8875 | pathogenic | -0.606 | Destabilizing | 0.826 | D | 0.528 | neutral | None | None | None | None | N |
| D/V | 0.8851 | likely_pathogenic | 0.8892 | pathogenic | -0.135 | Destabilizing | 0.879 | D | 0.638 | neutral | D | 0.55107154 | None | None | N |
| D/W | 0.9881 | likely_pathogenic | 0.9899 | pathogenic | -0.13 | Destabilizing | 0.991 | D | 0.673 | neutral | None | None | None | None | N |
| D/Y | 0.6986 | likely_pathogenic | 0.7182 | pathogenic | -0.109 | Destabilizing | 0.642 | D | 0.651 | neutral | N | 0.49312983 | 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.