Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8444 | 25555;25556;25557 | chr2:178717544;178717543;178717542 | chr2:179582271;179582270;179582269 |
| N2AB | 8127 | 24604;24605;24606 | chr2:178717544;178717543;178717542 | chr2:179582271;179582270;179582269 |
| N2A | 7200 | 21823;21824;21825 | chr2:178717544;178717543;178717542 | chr2:179582271;179582270;179582269 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs547641733  |
-0.835 | 0.966 | N | 0.47 | 0.331 | 0.360565625551 | gnomAD-2.1.1 | 8.17E-06 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| S/G | rs547641733 |
-0.835 | 0.966 | N | 0.47 | 0.331 | 0.360565625551 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs547641733 |
-0.835 | 0.966 | N | 0.47 | 0.331 | 0.360565625551 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/G | rs547641733 |
-0.835 | 0.966 | N | 0.47 | 0.331 | 0.360565625551 | gnomAD-4.0.0 | 1.2913E-05 | None | None | None | None | I | None | 5.08492E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.83017E-06 | 0 | 1.43373E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.102 | likely_benign | 0.0977 | benign | -0.66 | Destabilizing | 0.599 | D | 0.507 | neutral | None | None | None | None | I |
| S/C | 0.249 | likely_benign | 0.2277 | benign | -0.461 | Destabilizing | 1.0 | D | 0.552 | neutral | N | 0.507448023 | None | None | I |
| S/D | 0.6051 | likely_pathogenic | 0.6307 | pathogenic | -0.348 | Destabilizing | 0.961 | D | 0.481 | neutral | None | None | None | None | I |
| S/E | 0.6661 | likely_pathogenic | 0.6687 | pathogenic | -0.407 | Destabilizing | 0.478 | N | 0.393 | neutral | None | None | None | None | I |
| S/F | 0.263 | likely_benign | 0.2145 | benign | -1.156 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| S/G | 0.1364 | likely_benign | 0.1466 | benign | -0.818 | Destabilizing | 0.966 | D | 0.47 | neutral | N | 0.499432626 | None | None | I |
| S/H | 0.4433 | ambiguous | 0.4435 | ambiguous | -1.381 | Destabilizing | 0.999 | D | 0.56 | neutral | None | None | None | None | I |
| S/I | 0.2265 | likely_benign | 0.2178 | benign | -0.358 | Destabilizing | 1.0 | D | 0.63 | neutral | N | 0.499939605 | None | None | I |
| S/K | 0.7433 | likely_pathogenic | 0.7629 | pathogenic | -0.598 | Destabilizing | 0.974 | D | 0.473 | neutral | None | None | None | None | I |
| S/L | 0.1492 | likely_benign | 0.1309 | benign | -0.358 | Destabilizing | 0.995 | D | 0.599 | neutral | None | None | None | None | I |
| S/M | 0.2714 | likely_benign | 0.2552 | benign | 0.109 | Stabilizing | 1.0 | D | 0.55 | neutral | None | None | None | None | I |
| S/N | 0.1967 | likely_benign | 0.2118 | benign | -0.451 | Destabilizing | 0.055 | N | 0.395 | neutral | D | 0.534040979 | None | None | I |
| S/P | 0.6655 | likely_pathogenic | 0.6104 | pathogenic | -0.429 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | I |
| S/Q | 0.5668 | likely_pathogenic | 0.5759 | pathogenic | -0.776 | Destabilizing | 0.943 | D | 0.353 | neutral | None | None | None | None | I |
| S/R | 0.6285 | likely_pathogenic | 0.6548 | pathogenic | -0.366 | Destabilizing | 0.5 | D | 0.355 | neutral | N | 0.498408253 | None | None | I |
| S/T | 0.0875 | likely_benign | 0.085 | benign | -0.533 | Destabilizing | 0.812 | D | 0.503 | neutral | N | 0.487132466 | None | None | I |
| S/V | 0.222 | likely_benign | 0.2089 | benign | -0.429 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | I |
| S/W | 0.4999 | ambiguous | 0.4532 | ambiguous | -1.092 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| S/Y | 0.2993 | likely_benign | 0.2638 | benign | -0.825 | Destabilizing | 1.0 | D | 0.623 | 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.