Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25320 | 76183;76184;76185 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| N2AB | 23679 | 71260;71261;71262 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| N2A | 22752 | 68479;68480;68481 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| N2B | 16255 | 48988;48989;48990 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| Novex-1 | 16380 | 49363;49364;49365 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| Novex-2 | 16447 | 49564;49565;49566 | chr2:178570174;178570173;178570172 | chr2:179434901;179434900;179434899 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs772816442  |
-0.32 | 0.773 | N | 0.423 | 0.345 | 0.331365685468 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.36E-05 | 0 |
| S/A | rs772816442 |
-0.32 | 0.773 | N | 0.423 | 0.345 | 0.331365685468 | 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 |
| S/A | rs772816442 |
-0.32 | 0.773 | N | 0.423 | 0.345 | 0.331365685468 | gnomAD-4.0.0 | 2.2313E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.79748E-05 | 0 | 4.80446E-05 |
| S/P | rs772816442 |
-0.05 | 0.983 | D | 0.741 | 0.531 | 0.518752145996 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| S/P | rs772816442 |
-0.05 | 0.983 | D | 0.741 | 0.531 | 0.518752145996 | gnomAD-4.0.0 | 6.84311E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1441 | likely_benign | 0.147 | benign | -0.493 | Destabilizing | 0.773 | D | 0.423 | neutral | N | 0.501650082 | None | None | N |
| S/C | 0.1377 | likely_benign | 0.1719 | benign | -0.835 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/D | 0.9196 | likely_pathogenic | 0.9201 | pathogenic | -1.922 | Destabilizing | 0.845 | D | 0.426 | neutral | None | None | None | None | N |
| S/E | 0.9274 | likely_pathogenic | 0.9306 | pathogenic | -1.847 | Destabilizing | 0.033 | N | 0.334 | neutral | None | None | None | None | N |
| S/F | 0.4005 | ambiguous | 0.4417 | ambiguous | -0.723 | Destabilizing | 0.996 | D | 0.752 | deleterious | None | None | None | None | N |
| S/G | 0.1745 | likely_benign | 0.2122 | benign | -0.763 | Destabilizing | 0.916 | D | 0.42 | neutral | None | None | None | None | N |
| S/H | 0.6474 | likely_pathogenic | 0.6827 | pathogenic | -1.269 | Destabilizing | 0.997 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/I | 0.6734 | likely_pathogenic | 0.7011 | pathogenic | 0.129 | Stabilizing | 0.987 | D | 0.755 | deleterious | None | None | None | None | N |
| S/K | 0.9742 | likely_pathogenic | 0.9787 | pathogenic | -0.694 | Destabilizing | 0.845 | D | 0.465 | neutral | None | None | None | None | N |
| S/L | 0.3155 | likely_benign | 0.3495 | ambiguous | 0.129 | Stabilizing | 0.967 | D | 0.721 | prob.delet. | D | 0.531568396 | None | None | N |
| S/M | 0.3919 | ambiguous | 0.4369 | ambiguous | 0.292 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/N | 0.4441 | ambiguous | 0.4813 | ambiguous | -1.222 | Destabilizing | 0.916 | D | 0.503 | neutral | None | None | None | None | N |
| S/P | 0.9962 | likely_pathogenic | 0.9962 | pathogenic | -0.045 | Destabilizing | 0.983 | D | 0.741 | deleterious | D | 0.542924702 | None | None | N |
| S/Q | 0.8516 | likely_pathogenic | 0.871 | pathogenic | -1.329 | Destabilizing | 0.95 | D | 0.601 | neutral | None | None | None | None | N |
| S/R | 0.9511 | likely_pathogenic | 0.958 | pathogenic | -0.638 | Destabilizing | 0.975 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/T | 0.1524 | likely_benign | 0.1643 | benign | -0.895 | Destabilizing | 0.892 | D | 0.439 | neutral | N | 0.516908295 | None | None | N |
| S/V | 0.5943 | likely_pathogenic | 0.633 | pathogenic | -0.045 | Destabilizing | 0.987 | D | 0.727 | prob.delet. | None | None | None | None | N |
| S/W | 0.7343 | likely_pathogenic | 0.7519 | pathogenic | -0.928 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/Y | 0.4193 | ambiguous | 0.4506 | ambiguous | -0.498 | Destabilizing | 0.996 | D | 0.753 | deleterious | None | None | 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.