Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14797 | 44614;44615;44616 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| N2AB | 13156 | 39691;39692;39693 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| N2A | 12229 | 36910;36911;36912 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| N2B | 5732 | 17419;17420;17421 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| Novex-1 | 5857 | 17794;17795;17796 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| Novex-2 | 5924 | 17995;17996;17997 | chr2:178629336;178629335;178629334 | chr2:179494063;179494062;179494061 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs876658060  |
None | 0.99 | D | 0.585 | 0.264 | 0.571625278582 | gnomAD-4.0.0 | 1.59354E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86218E-06 | 0 | 0 |
| Y/H | None | None | 0.963 | N | 0.555 | 0.39 | 0.448794319169 | gnomAD-4.0.0 | 1.59354E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86211E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6593 | likely_pathogenic | 0.7572 | pathogenic | -2.88 | Highly Destabilizing | 0.617 | D | 0.579 | neutral | None | None | None | None | N |
| Y/C | 0.2259 | likely_benign | 0.273 | benign | -1.364 | Destabilizing | 0.99 | D | 0.585 | neutral | D | 0.528602013 | None | None | N |
| Y/D | 0.5831 | likely_pathogenic | 0.7149 | pathogenic | -1.845 | Destabilizing | 0.963 | D | 0.609 | neutral | D | 0.568795454 | None | None | N |
| Y/E | 0.7399 | likely_pathogenic | 0.8333 | pathogenic | -1.741 | Destabilizing | 0.972 | D | 0.581 | neutral | None | None | None | None | N |
| Y/F | 0.0579 | likely_benign | 0.0551 | benign | -1.261 | Destabilizing | 0.001 | N | 0.218 | neutral | N | 0.410904972 | None | None | N |
| Y/G | 0.6691 | likely_pathogenic | 0.7474 | pathogenic | -3.213 | Highly Destabilizing | 0.766 | D | 0.581 | neutral | None | None | None | None | N |
| Y/H | 0.1759 | likely_benign | 0.211 | benign | -1.444 | Destabilizing | 0.963 | D | 0.555 | neutral | N | 0.47266573 | None | None | N |
| Y/I | 0.3813 | ambiguous | 0.4708 | ambiguous | -1.836 | Destabilizing | 0.447 | N | 0.531 | neutral | None | None | None | None | N |
| Y/K | 0.6183 | likely_pathogenic | 0.7289 | pathogenic | -1.504 | Destabilizing | 0.92 | D | 0.581 | neutral | None | None | None | None | N |
| Y/L | 0.4214 | ambiguous | 0.4854 | ambiguous | -1.836 | Destabilizing | 0.25 | N | 0.52 | neutral | None | None | None | None | N |
| Y/M | 0.5017 | ambiguous | 0.5581 | ambiguous | -1.457 | Destabilizing | 0.92 | D | 0.56 | neutral | None | None | None | None | N |
| Y/N | 0.2787 | likely_benign | 0.3753 | ambiguous | -1.815 | Destabilizing | 0.963 | D | 0.593 | neutral | N | 0.503937623 | None | None | N |
| Y/P | 0.988 | likely_pathogenic | 0.9922 | pathogenic | -2.185 | Highly Destabilizing | 0.972 | D | 0.626 | neutral | None | None | None | None | N |
| Y/Q | 0.5503 | ambiguous | 0.6538 | pathogenic | -1.813 | Destabilizing | 0.972 | D | 0.569 | neutral | None | None | None | None | N |
| Y/R | 0.5216 | ambiguous | 0.6195 | pathogenic | -0.918 | Destabilizing | 0.92 | D | 0.592 | neutral | None | None | None | None | N |
| Y/S | 0.3436 | ambiguous | 0.4398 | ambiguous | -2.375 | Highly Destabilizing | 0.712 | D | 0.56 | neutral | N | 0.459059873 | None | None | N |
| Y/T | 0.5265 | ambiguous | 0.6282 | pathogenic | -2.177 | Highly Destabilizing | 0.766 | D | 0.566 | neutral | None | None | None | None | N |
| Y/V | 0.3625 | ambiguous | 0.4438 | ambiguous | -2.185 | Highly Destabilizing | 0.447 | N | 0.555 | neutral | None | None | None | None | N |
| Y/W | 0.3948 | ambiguous | 0.3807 | ambiguous | -0.662 | Destabilizing | 0.972 | D | 0.552 | 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.