Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2174 | 6745;6746;6747 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| N2AB | 2174 | 6745;6746;6747 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| N2A | 2174 | 6745;6746;6747 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| N2B | 2128 | 6607;6608;6609 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| Novex-1 | 2128 | 6607;6608;6609 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| Novex-2 | 2128 | 6607;6608;6609 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
| Novex-3 | 2174 | 6745;6746;6747 | chr2:178775191;178775190;178775189 | chr2:179639918;179639917;179639916 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1414401674  |
-1.184 | 0.713 | N | 0.525 | 0.13 | 0.304108284078 | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs1414401674 |
-1.184 | 0.713 | N | 0.525 | 0.13 | 0.304108284078 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | N | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15969E-05 | 0 |
| I/V | rs1171508892 |
-1.425 | 0.001 | N | 0.309 | 0.089 | 0.245660935333 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1171508892 |
-1.425 | 0.001 | N | 0.309 | 0.089 | 0.245660935333 | gnomAD-4.0.0 | 3.18193E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4457 | ambiguous | 0.4734 | ambiguous | -0.819 | Destabilizing | 0.32 | N | 0.477 | neutral | None | None | None | None | N |
| I/C | 0.729 | likely_pathogenic | 0.7469 | pathogenic | -0.919 | Destabilizing | 0.962 | D | 0.535 | neutral | None | None | None | None | N |
| I/D | 0.8389 | likely_pathogenic | 0.8637 | pathogenic | -0.257 | Destabilizing | 0.87 | D | 0.645 | neutral | None | None | None | None | N |
| I/E | 0.7474 | likely_pathogenic | 0.7755 | pathogenic | -0.289 | Destabilizing | 0.87 | D | 0.649 | neutral | None | None | None | None | N |
| I/F | 0.2362 | likely_benign | 0.2413 | benign | -0.606 | Destabilizing | 0.713 | D | 0.533 | neutral | N | 0.388169068 | None | None | N |
| I/G | 0.7435 | likely_pathogenic | 0.7741 | pathogenic | -1.033 | Destabilizing | 0.87 | D | 0.643 | neutral | None | None | None | None | N |
| I/H | 0.5833 | likely_pathogenic | 0.6169 | pathogenic | -0.179 | Destabilizing | 0.987 | D | 0.634 | neutral | None | None | None | None | N |
| I/K | 0.4783 | ambiguous | 0.5182 | ambiguous | -0.534 | Destabilizing | 0.87 | D | 0.649 | neutral | None | None | None | None | N |
| I/L | 0.1198 | likely_benign | 0.1271 | benign | -0.34 | Destabilizing | 0.06 | N | 0.373 | neutral | N | 0.349399269 | None | None | N |
| I/M | 0.1268 | likely_benign | 0.132 | benign | -0.624 | Destabilizing | 0.713 | D | 0.525 | neutral | N | 0.391502997 | None | None | N |
| I/N | 0.3775 | ambiguous | 0.4208 | ambiguous | -0.457 | Destabilizing | 0.939 | D | 0.653 | neutral | N | 0.392010571 | None | None | N |
| I/P | 0.5683 | likely_pathogenic | 0.5922 | pathogenic | -0.469 | Destabilizing | 0.953 | D | 0.651 | neutral | None | None | None | None | N |
| I/Q | 0.5208 | ambiguous | 0.5537 | ambiguous | -0.57 | Destabilizing | 0.953 | D | 0.649 | neutral | None | None | None | None | N |
| I/R | 0.4014 | ambiguous | 0.4417 | ambiguous | -0.061 | Destabilizing | 0.87 | D | 0.653 | neutral | None | None | None | None | N |
| I/S | 0.4459 | ambiguous | 0.4884 | ambiguous | -0.965 | Destabilizing | 0.713 | D | 0.56 | neutral | N | 0.39036935 | None | None | N |
| I/T | 0.3526 | ambiguous | 0.3711 | ambiguous | -0.871 | Destabilizing | 0.415 | N | 0.467 | neutral | N | 0.38985695 | None | None | N |
| I/V | 0.0861 | likely_benign | 0.0835 | benign | -0.469 | Destabilizing | 0.001 | N | 0.309 | neutral | N | 0.343703068 | None | None | N |
| I/W | 0.8461 | likely_pathogenic | 0.8462 | pathogenic | -0.62 | Destabilizing | 0.987 | D | 0.623 | neutral | None | None | None | None | N |
| I/Y | 0.5726 | likely_pathogenic | 0.6016 | pathogenic | -0.394 | Destabilizing | 0.87 | D | 0.521 | neutral | 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.