Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19458 | 58597;58598;58599 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| N2AB | 17817 | 53674;53675;53676 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| N2A | 16890 | 50893;50894;50895 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| N2B | 10393 | 31402;31403;31404 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| Novex-1 | 10518 | 31777;31778;31779 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| Novex-2 | 10585 | 31978;31979;31980 | chr2:178594021;178594020;178594019 | chr2:179458748;179458747;179458746 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs867494706  |
None | 0.001 | N | 0.607 | 0.208 | 0.448597761117 | gnomAD-4.0.0 | 1.59171E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85909E-06 | 0 | 0 |
| C/W | rs777855018 |
None | 0.828 | N | 0.635 | 0.19 | 0.514923749907 | gnomAD-4.0.0 | 1.59172E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88232E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2297 | likely_benign | 0.2486 | benign | -0.915 | Destabilizing | 0.007 | N | 0.397 | neutral | None | None | None | None | N |
| C/D | 0.6021 | likely_pathogenic | 0.6155 | pathogenic | -1.105 | Destabilizing | 0.038 | N | 0.665 | neutral | None | None | None | None | N |
| C/E | 0.5499 | ambiguous | 0.5697 | pathogenic | -0.848 | Destabilizing | 0.038 | N | 0.635 | neutral | None | None | None | None | N |
| C/F | 0.1406 | likely_benign | 0.1497 | benign | -0.492 | Destabilizing | 0.171 | N | 0.643 | neutral | N | 0.47771711 | None | None | N |
| C/G | 0.1605 | likely_benign | 0.1653 | benign | -1.269 | Destabilizing | None | N | 0.473 | neutral | N | 0.451840017 | None | None | N |
| C/H | 0.2862 | likely_benign | 0.2996 | benign | -1.528 | Destabilizing | 0.356 | N | 0.647 | neutral | None | None | None | None | N |
| C/I | 0.2524 | likely_benign | 0.2779 | benign | 0.045 | Stabilizing | 0.038 | N | 0.641 | neutral | None | None | None | None | N |
| C/K | 0.5355 | ambiguous | 0.5583 | ambiguous | -0.176 | Destabilizing | 0.038 | N | 0.615 | neutral | None | None | None | None | N |
| C/L | 0.2706 | likely_benign | 0.2932 | benign | 0.045 | Stabilizing | 0.016 | N | 0.574 | neutral | None | None | None | None | N |
| C/M | 0.3387 | likely_benign | 0.3808 | ambiguous | 0.538 | Stabilizing | 0.007 | N | 0.531 | neutral | None | None | None | None | N |
| C/N | 0.3356 | likely_benign | 0.3867 | ambiguous | -1.005 | Destabilizing | 0.038 | N | 0.663 | neutral | None | None | None | None | N |
| C/P | 0.987 | likely_pathogenic | 0.9871 | pathogenic | -0.254 | Destabilizing | 0.214 | N | 0.679 | prob.neutral | None | None | None | None | N |
| C/Q | 0.3534 | ambiguous | 0.3809 | ambiguous | -0.449 | Destabilizing | 0.214 | N | 0.677 | prob.neutral | None | None | None | None | N |
| C/R | 0.2465 | likely_benign | 0.2481 | benign | -0.873 | Destabilizing | 0.001 | N | 0.607 | neutral | N | 0.421823754 | None | None | N |
| C/S | 0.1479 | likely_benign | 0.1669 | benign | -1.153 | Destabilizing | None | N | 0.384 | neutral | N | 0.411318759 | None | None | N |
| C/T | 0.1758 | likely_benign | 0.2098 | benign | -0.71 | Destabilizing | None | N | 0.349 | neutral | None | None | None | None | N |
| C/V | 0.2134 | likely_benign | 0.2357 | benign | -0.254 | Destabilizing | 0.016 | N | 0.563 | neutral | None | None | None | None | N |
| C/W | 0.3742 | ambiguous | 0.3643 | ambiguous | -0.949 | Destabilizing | 0.828 | D | 0.635 | neutral | N | 0.455611041 | None | None | N |
| C/Y | 0.1908 | likely_benign | 0.192 | benign | -0.64 | Destabilizing | 0.295 | N | 0.643 | neutral | N | 0.469828345 | 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.