Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19798 | 59617;59618;59619 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| N2AB | 18157 | 54694;54695;54696 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| N2A | 17230 | 51913;51914;51915 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| N2B | 10733 | 32422;32423;32424 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| Novex-1 | 10858 | 32797;32798;32799 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| Novex-2 | 10925 | 32998;32999;33000 | chr2:178592613;178592612;178592611 | chr2:179457340;179457339;179457338 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs772501285  |
-0.71 | 0.966 | D | 0.456 | 0.366 | 0.551838628669 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs772501285 |
-0.71 | 0.966 | D | 0.456 | 0.366 | 0.551838628669 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-05 | 0 |
| I/N | None | None | 0.989 | N | 0.529 | 0.576 | 0.789076550681 | gnomAD-4.0.0 | 1.59213E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 0 |
| I/T | None | None | 0.801 | N | 0.351 | 0.358 | 0.737149919481 | gnomAD-4.0.0 | 1.59213E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-05 |
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 | 0.775 | likely_pathogenic | 0.6686 | pathogenic | -2.203 | Highly Destabilizing | 0.029 | N | 0.167 | neutral | None | None | None | None | I |
| I/C | 0.7783 | likely_pathogenic | 0.7196 | pathogenic | -1.394 | Destabilizing | 0.991 | D | 0.437 | neutral | None | None | None | None | I |
| I/D | 0.9825 | likely_pathogenic | 0.9766 | pathogenic | -2.038 | Highly Destabilizing | 0.974 | D | 0.535 | neutral | None | None | None | None | I |
| I/E | 0.947 | likely_pathogenic | 0.9413 | pathogenic | -1.939 | Destabilizing | 0.974 | D | 0.52 | neutral | None | None | None | None | I |
| I/F | 0.4384 | ambiguous | 0.3897 | ambiguous | -1.378 | Destabilizing | 0.934 | D | 0.449 | neutral | N | 0.512550986 | None | None | I |
| I/G | 0.9384 | likely_pathogenic | 0.9078 | pathogenic | -2.633 | Highly Destabilizing | 0.728 | D | 0.475 | neutral | None | None | None | None | I |
| I/H | 0.9053 | likely_pathogenic | 0.8885 | pathogenic | -1.946 | Destabilizing | 0.998 | D | 0.513 | neutral | None | None | None | None | I |
| I/K | 0.8455 | likely_pathogenic | 0.8521 | pathogenic | -1.645 | Destabilizing | 0.949 | D | 0.531 | neutral | None | None | None | None | I |
| I/L | 0.1871 | likely_benign | 0.1729 | benign | -1.023 | Destabilizing | 0.267 | N | 0.283 | neutral | N | 0.467989345 | None | None | I |
| I/M | 0.221 | likely_benign | 0.1825 | benign | -0.839 | Destabilizing | 0.966 | D | 0.456 | neutral | D | 0.526288287 | None | None | I |
| I/N | 0.8181 | likely_pathogenic | 0.7798 | pathogenic | -1.617 | Destabilizing | 0.989 | D | 0.529 | neutral | N | 0.490420179 | None | None | I |
| I/P | 0.9745 | likely_pathogenic | 0.9738 | pathogenic | -1.39 | Destabilizing | 0.974 | D | 0.537 | neutral | None | None | None | None | I |
| I/Q | 0.8486 | likely_pathogenic | 0.8348 | pathogenic | -1.683 | Destabilizing | 0.991 | D | 0.533 | neutral | None | None | None | None | I |
| I/R | 0.7766 | likely_pathogenic | 0.7866 | pathogenic | -1.138 | Destabilizing | 0.974 | D | 0.524 | neutral | None | None | None | None | I |
| I/S | 0.7888 | likely_pathogenic | 0.7298 | pathogenic | -2.284 | Highly Destabilizing | 0.669 | D | 0.404 | neutral | N | 0.48965971 | None | None | I |
| I/T | 0.6932 | likely_pathogenic | 0.5887 | pathogenic | -2.064 | Highly Destabilizing | 0.801 | D | 0.351 | neutral | N | 0.509433323 | None | None | I |
| I/V | 0.0968 | likely_benign | 0.0804 | benign | -1.39 | Destabilizing | 0.005 | N | 0.132 | neutral | N | 0.378575275 | None | None | I |
| I/W | 0.9412 | likely_pathogenic | 0.9422 | pathogenic | -1.611 | Destabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | I |
| I/Y | 0.8509 | likely_pathogenic | 0.8454 | pathogenic | -1.371 | Destabilizing | 0.974 | D | 0.444 | 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.