Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1567 | 4924;4925;4926 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| N2AB | 1567 | 4924;4925;4926 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| N2A | 1567 | 4924;4925;4926 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| N2B | 1521 | 4786;4787;4788 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| Novex-1 | 1521 | 4786;4787;4788 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| Novex-2 | 1521 | 4786;4787;4788 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
| Novex-3 | 1567 | 4924;4925;4926 | chr2:178777264;178777263;178777262 | chr2:179641991;179641990;179641989 |
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/K | None | None | 0.773 | N | 0.583 | 0.494 | 0.794301526555 | gnomAD-4.0.0 | 1.59077E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85678E-06 | 0 | 0 |
| I/R | None | None | 0.773 | N | 0.585 | 0.506 | 0.797486517669 | gnomAD-4.0.0 | 1.59077E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85678E-06 | 0 | 0 |
| I/T | rs145957227  |
-1.779 | 0.324 | N | 0.413 | 0.267 | None | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| I/T | rs145957227 |
-1.779 | 0.324 | N | 0.413 | 0.267 | 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 |
| I/T | rs145957227 |
-1.779 | 0.324 | N | 0.413 | 0.267 | None | gnomAD-4.0.0 | 7.68423E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43521E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3584 | ambiguous | 0.3648 | ambiguous | -2.059 | Highly Destabilizing | 0.116 | N | 0.368 | neutral | None | None | None | None | N |
| I/C | 0.6288 | likely_pathogenic | 0.6103 | pathogenic | -1.624 | Destabilizing | 0.944 | D | 0.52 | neutral | None | None | None | None | N |
| I/D | 0.9056 | likely_pathogenic | 0.9114 | pathogenic | -1.698 | Destabilizing | 0.818 | D | 0.584 | neutral | None | None | None | None | N |
| I/E | 0.776 | likely_pathogenic | 0.7847 | pathogenic | -1.652 | Destabilizing | 0.818 | D | 0.579 | neutral | None | None | None | None | N |
| I/F | 0.2821 | likely_benign | 0.3029 | benign | -1.497 | Destabilizing | 0.69 | D | 0.505 | neutral | None | None | None | None | N |
| I/G | 0.686 | likely_pathogenic | 0.6937 | pathogenic | -2.433 | Highly Destabilizing | 0.563 | D | 0.54 | neutral | None | None | None | None | N |
| I/H | 0.7611 | likely_pathogenic | 0.763 | pathogenic | -1.638 | Destabilizing | 0.981 | D | 0.545 | neutral | None | None | None | None | N |
| I/K | 0.6347 | likely_pathogenic | 0.6573 | pathogenic | -1.442 | Destabilizing | 0.773 | D | 0.583 | neutral | N | 0.507029907 | None | None | N |
| I/L | 0.141 | likely_benign | 0.1451 | benign | -1.073 | Destabilizing | 0.018 | N | 0.272 | neutral | N | 0.473030848 | None | None | N |
| I/M | 0.1263 | likely_benign | 0.1353 | benign | -0.983 | Destabilizing | 0.627 | D | 0.529 | neutral | N | 0.51573515 | None | None | N |
| I/N | 0.555 | ambiguous | 0.5869 | pathogenic | -1.368 | Destabilizing | 0.932 | D | 0.58 | neutral | None | None | None | None | N |
| I/P | 0.9531 | likely_pathogenic | 0.957 | pathogenic | -1.373 | Destabilizing | 0.932 | D | 0.584 | neutral | None | None | None | None | N |
| I/Q | 0.6327 | likely_pathogenic | 0.6357 | pathogenic | -1.528 | Destabilizing | 0.932 | D | 0.589 | neutral | None | None | None | None | N |
| I/R | 0.5319 | ambiguous | 0.5563 | ambiguous | -0.878 | Destabilizing | 0.773 | D | 0.585 | neutral | N | 0.499037676 | None | None | N |
| I/S | 0.4398 | ambiguous | 0.4614 | ambiguous | -2.066 | Highly Destabilizing | 0.388 | N | 0.494 | neutral | None | None | None | None | N |
| I/T | 0.2562 | likely_benign | 0.2648 | benign | -1.895 | Destabilizing | 0.324 | N | 0.413 | neutral | N | 0.489068307 | None | None | N |
| I/V | 0.0556 | likely_benign | 0.0563 | benign | -1.373 | Destabilizing | None | N | 0.121 | neutral | N | 0.330098735 | None | None | N |
| I/W | 0.9025 | likely_pathogenic | 0.8933 | pathogenic | -1.58 | Destabilizing | 0.981 | D | 0.559 | neutral | None | None | None | None | N |
| I/Y | 0.7114 | likely_pathogenic | 0.7147 | pathogenic | -1.348 | Destabilizing | 0.818 | D | 0.557 | 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.