Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21453 | 64582;64583;64584 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| N2AB | 19812 | 59659;59660;59661 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| N2A | 18885 | 56878;56879;56880 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| N2B | 12388 | 37387;37388;37389 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| Novex-1 | 12513 | 37762;37763;37764 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| Novex-2 | 12580 | 37963;37964;37965 | chr2:178586544;178586543;178586542 | chr2:179451271;179451270;179451269 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1014690727  |
-1.841 | 0.722 | N | 0.591 | 0.198 | 0.341934017632 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1014690727 |
-1.841 | 0.722 | N | 0.591 | 0.198 | 0.341934017632 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs1014690727 |
-1.841 | 0.722 | N | 0.591 | 0.198 | 0.341934017632 | gnomAD-4.0.0 | 8.97411E-06 | None | None | None | None | I | None | 6.76613E-05 | 0 | None | 0 | 4.85838E-05 | None | 0 | 0 | 2.39524E-06 | 0 | 0 |
| R/K | None | None | 0.008 | N | 0.227 | 0.088 | None | gnomAD-4.0.0 | 1.36894E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99776E-07 | 0 | 1.65744E-05 |
| R/T | rs765575975 |
None | 0.722 | N | 0.555 | 0.144 | 0.280181792013 | gnomAD-4.0.0 | 1.36894E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79955E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7047 | likely_pathogenic | 0.6287 | pathogenic | -1.003 | Destabilizing | 0.633 | D | 0.566 | neutral | None | None | None | None | I |
| R/C | 0.4741 | ambiguous | 0.3898 | ambiguous | -0.946 | Destabilizing | 0.996 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/D | 0.9551 | likely_pathogenic | 0.935 | pathogenic | -0.138 | Destabilizing | 0.923 | D | 0.631 | neutral | None | None | None | None | I |
| R/E | 0.7745 | likely_pathogenic | 0.7073 | pathogenic | 0.039 | Stabilizing | 0.633 | D | 0.403 | neutral | None | None | None | None | I |
| R/F | 0.9205 | likely_pathogenic | 0.8863 | pathogenic | -0.438 | Destabilizing | 0.923 | D | 0.688 | prob.neutral | None | None | None | None | I |
| R/G | 0.6978 | likely_pathogenic | 0.6231 | pathogenic | -1.376 | Destabilizing | 0.722 | D | 0.591 | neutral | N | 0.475743958 | None | None | I |
| R/H | 0.4359 | ambiguous | 0.3619 | ambiguous | -1.528 | Destabilizing | 0.961 | D | 0.518 | neutral | None | None | None | None | I |
| R/I | 0.7204 | likely_pathogenic | 0.6218 | pathogenic | 0.032 | Stabilizing | 0.018 | N | 0.572 | neutral | N | 0.505720148 | None | None | I |
| R/K | 0.248 | likely_benign | 0.2127 | benign | -0.971 | Destabilizing | 0.008 | N | 0.227 | neutral | N | 0.50554679 | None | None | I |
| R/L | 0.673 | likely_pathogenic | 0.5883 | pathogenic | 0.032 | Stabilizing | 0.633 | D | 0.611 | neutral | None | None | None | None | I |
| R/M | 0.7002 | likely_pathogenic | 0.5864 | pathogenic | -0.44 | Destabilizing | 0.923 | D | 0.64 | neutral | None | None | None | None | I |
| R/N | 0.9316 | likely_pathogenic | 0.8942 | pathogenic | -0.583 | Destabilizing | 0.923 | D | 0.481 | neutral | None | None | None | None | I |
| R/P | 0.9753 | likely_pathogenic | 0.9697 | pathogenic | -0.294 | Destabilizing | 0.961 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/Q | 0.2658 | likely_benign | 0.2196 | benign | -0.578 | Destabilizing | 0.858 | D | 0.523 | neutral | None | None | None | None | I |
| R/S | 0.8396 | likely_pathogenic | 0.7808 | pathogenic | -1.381 | Destabilizing | 0.565 | D | 0.536 | neutral | N | 0.370757429 | None | None | I |
| R/T | 0.5981 | likely_pathogenic | 0.4818 | ambiguous | -0.996 | Destabilizing | 0.722 | D | 0.555 | neutral | N | 0.436473494 | None | None | I |
| R/V | 0.6609 | likely_pathogenic | 0.5684 | pathogenic | -0.294 | Destabilizing | 0.633 | D | 0.597 | neutral | None | None | None | None | I |
| R/W | 0.6237 | likely_pathogenic | 0.5481 | ambiguous | -0.009 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/Y | 0.8497 | likely_pathogenic | 0.7928 | pathogenic | 0.214 | Stabilizing | 0.987 | D | 0.675 | prob.neutral | None | None | None | None | I |
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.