Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6434 | 19525;19526;19527 | chr2:178728626;178728625;178728624 | chr2:179593353;179593352;179593351 |
| N2AB | 6117 | 18574;18575;18576 | chr2:178728626;178728625;178728624 | chr2:179593353;179593352;179593351 |
| N2A | 5190 | 15793;15794;15795 | chr2:178728626;178728625;178728624 | chr2:179593353;179593352;179593351 |
| 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 | rs1378850655  |
-0.62 | 0.549 | N | 0.313 | 0.28 | 0.219573609325 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66722E-04 |
| S/G | rs1378850655 |
-0.62 | 0.549 | N | 0.313 | 0.28 | 0.219573609325 | gnomAD-4.0.0 | 1.59252E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0281E-05 |
| S/N | rs11888217 |
-0.011 | 0.549 | N | 0.375 | 0.249 | None | gnomAD-2.1.1 | 7.12741E-02 | None | None | None | None | N | None | 8.25327E-02 | 1.85366E-01 | None | 3.66893E-02 | 2.68097E-02 | None | 1.74696E-01 | None | 5.57916E-02 | 2.63348E-02 | 5.67476E-02 |
| S/N | rs11888217 |
-0.011 | 0.549 | N | 0.375 | 0.249 | None | gnomAD-3.1.2 | 5.95512E-02 | None | None | None | None | N | None | 8.20535E-02 | 1.38914E-01 | 4.27632E-02 | 3.22767E-02 | 2.41406E-02 | None | 5.72533E-02 | 4.43038E-02 | 2.5575E-02 | 1.6722E-01 | 4.58453E-02 |
| S/N | rs11888217 |
-0.011 | 0.549 | N | 0.375 | 0.249 | None | 1000 genomes | 9.32508E-02 | None | None | None | None | N | None | 8.7E-02 | 1.513E-01 | None | None | 2.38E-02 | 3.58E-02 | None | None | None | 1.912E-01 | None |
| S/N | rs11888217 |
-0.011 | 0.549 | N | 0.375 | 0.249 | None | gnomAD-4.0.0 | 4.38879E-02 | None | None | None | None | N | None | 8.29644E-02 | 1.71905E-01 | None | 3.52893E-02 | 1.39838E-02 | None | 5.78162E-02 | 5.00165E-02 | 2.58051E-02 | 1.66403E-01 | 4.7841E-02 |
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 | 0.1067 | likely_benign | 0.1 | benign | -0.513 | Destabilizing | 0.127 | N | 0.249 | neutral | None | None | None | None | N |
| S/C | 0.2907 | likely_benign | 0.2022 | benign | -0.273 | Destabilizing | 0.99 | D | 0.388 | neutral | D | 0.524702905 | None | None | N |
| S/D | 0.4837 | ambiguous | 0.4158 | ambiguous | -0.179 | Destabilizing | 0.617 | D | 0.341 | neutral | None | None | None | None | N |
| S/E | 0.6201 | likely_pathogenic | 0.5551 | ambiguous | -0.251 | Destabilizing | 0.617 | D | 0.285 | neutral | None | None | None | None | N |
| S/F | 0.2485 | likely_benign | 0.203 | benign | -0.954 | Destabilizing | 0.92 | D | 0.503 | neutral | None | None | None | None | N |
| S/G | 0.1287 | likely_benign | 0.1231 | benign | -0.677 | Destabilizing | 0.549 | D | 0.313 | neutral | N | 0.509952784 | None | None | N |
| S/H | 0.37 | ambiguous | 0.3115 | benign | -1.214 | Destabilizing | 0.992 | D | 0.387 | neutral | None | None | None | None | N |
| S/I | 0.1976 | likely_benign | 0.1668 | benign | -0.201 | Destabilizing | 0.379 | N | 0.403 | neutral | N | 0.491443682 | None | None | N |
| S/K | 0.7096 | likely_pathogenic | 0.6405 | pathogenic | -0.659 | Destabilizing | 0.617 | D | 0.281 | neutral | None | None | None | None | N |
| S/L | 0.1541 | likely_benign | 0.1298 | benign | -0.201 | Destabilizing | 0.25 | N | 0.367 | neutral | None | None | None | None | N |
| S/M | 0.2521 | likely_benign | 0.232 | benign | 0.167 | Stabilizing | 0.92 | D | 0.403 | neutral | None | None | None | None | N |
| S/N | 0.1674 | likely_benign | 0.1503 | benign | -0.397 | Destabilizing | 0.549 | D | 0.375 | neutral | N | 0.50178603 | None | None | N |
| S/P | 0.9331 | likely_pathogenic | 0.8871 | pathogenic | -0.274 | Destabilizing | 0.92 | D | 0.381 | neutral | None | None | None | None | N |
| S/Q | 0.5452 | ambiguous | 0.4928 | ambiguous | -0.664 | Destabilizing | 0.92 | D | 0.396 | neutral | None | None | None | None | N |
| S/R | 0.6129 | likely_pathogenic | 0.524 | ambiguous | -0.419 | Destabilizing | 0.81 | D | 0.394 | neutral | N | 0.487276172 | None | None | N |
| S/T | 0.085 | likely_benign | 0.0821 | benign | -0.464 | Destabilizing | 0.002 | N | 0.101 | neutral | N | 0.471912298 | None | None | N |
| S/V | 0.2144 | likely_benign | 0.1875 | benign | -0.274 | Destabilizing | 0.009 | N | 0.23 | neutral | None | None | None | None | N |
| S/W | 0.4839 | ambiguous | 0.4007 | ambiguous | -0.936 | Destabilizing | 0.992 | D | 0.535 | neutral | None | None | None | None | N |
| S/Y | 0.2399 | likely_benign | 0.1838 | benign | -0.682 | Destabilizing | 0.972 | D | 0.499 | 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.