Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2755 | 8488;8489;8490 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| N2AB | 2755 | 8488;8489;8490 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| N2A | 2755 | 8488;8489;8490 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| N2B | 2709 | 8350;8351;8352 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| Novex-1 | 2709 | 8350;8351;8352 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| Novex-2 | 2709 | 8350;8351;8352 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
| Novex-3 | 2755 | 8488;8489;8490 | chr2:178770529;178770528;178770527 | chr2:179635256;179635255;179635254 |
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/L | rs749379860  |
-0.572 | 0.025 | D | 0.293 | 0.12 | 0.430579932962 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1235358964 |
-0.719 | 0.055 | N | 0.349 | 0.175 | 0.50557994651 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1235358964 |
-0.719 | 0.055 | N | 0.349 | 0.175 | 0.50557994651 | gnomAD-4.0.0 | 1.5905E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs2091308831 |
None | 0.859 | D | 0.715 | 0.678 | 0.846318057021 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs2091308831 |
None | 0.859 | D | 0.715 | 0.678 | 0.846318057021 | gnomAD-4.0.0 | 3.04473E-06 | None | None | None | None | N | None | 0 | 6.15385E-05 | None | 0 | 0 | None | 0 | 0 | 1.20492E-06 | 4.6966E-05 | 0 |
| I/V | rs749379860 |
None | None | N | 0.165 | 0.064 | 0.292062946507 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.3573 | ambiguous | 0.4901 | ambiguous | -1.723 | Destabilizing | 0.157 | N | 0.542 | neutral | None | None | None | None | N |
| I/C | 0.714 | likely_pathogenic | 0.8025 | pathogenic | -1.189 | Destabilizing | 0.909 | D | 0.619 | neutral | None | None | None | None | N |
| I/D | 0.7355 | likely_pathogenic | 0.8677 | pathogenic | -0.689 | Destabilizing | 0.726 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/E | 0.6143 | likely_pathogenic | 0.7697 | pathogenic | -0.649 | Destabilizing | 0.726 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/F | 0.144 | likely_benign | 0.1719 | benign | -1.219 | Destabilizing | 0.497 | N | 0.521 | neutral | D | 0.578860075 | None | None | N |
| I/G | 0.6895 | likely_pathogenic | 0.8121 | pathogenic | -2.082 | Highly Destabilizing | 0.726 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/H | 0.5791 | likely_pathogenic | 0.7192 | pathogenic | -1.287 | Destabilizing | 0.968 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/K | 0.465 | ambiguous | 0.6184 | pathogenic | -1.017 | Destabilizing | 0.726 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/L | 0.1301 | likely_benign | 0.1474 | benign | -0.797 | Destabilizing | 0.025 | N | 0.293 | neutral | D | 0.545588311 | None | None | N |
| I/M | 0.1262 | likely_benign | 0.139 | benign | -0.708 | Destabilizing | 0.055 | N | 0.349 | neutral | N | 0.515338517 | None | None | N |
| I/N | 0.341 | ambiguous | 0.4912 | ambiguous | -0.888 | Destabilizing | 0.859 | D | 0.715 | prob.delet. | D | 0.67520401 | None | None | N |
| I/P | 0.7613 | likely_pathogenic | 0.8677 | pathogenic | -1.075 | Destabilizing | 0.89 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5175 | ambiguous | 0.65 | pathogenic | -0.98 | Destabilizing | 0.726 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/R | 0.3792 | ambiguous | 0.5176 | ambiguous | -0.556 | Destabilizing | 0.726 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/S | 0.348 | ambiguous | 0.488 | ambiguous | -1.625 | Destabilizing | 0.497 | N | 0.604 | neutral | D | 0.61128102 | None | None | N |
| I/T | 0.2882 | likely_benign | 0.3894 | ambiguous | -1.447 | Destabilizing | 0.124 | N | 0.561 | neutral | D | 0.609982464 | None | None | N |
| I/V | 0.0744 | likely_benign | 0.0867 | benign | -1.075 | Destabilizing | None | N | 0.165 | neutral | N | 0.503083732 | None | None | N |
| I/W | 0.8225 | likely_pathogenic | 0.8772 | pathogenic | -1.271 | Destabilizing | 0.968 | D | 0.745 | deleterious | None | None | None | None | N |
| I/Y | 0.4862 | ambiguous | 0.597 | pathogenic | -1.032 | Destabilizing | 0.726 | D | 0.619 | 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.