Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5059 | 15400;15401;15402 | chr2:178734749;178734748;178734747 | chr2:179599476;179599475;179599474 |
| N2AB | 4742 | 14449;14450;14451 | chr2:178734749;178734748;178734747 | chr2:179599476;179599475;179599474 |
| N2A | 3815 | 11668;11669;11670 | chr2:178734749;178734748;178734747 | chr2:179599476;179599475;179599474 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs74607159  |
None | 0.015 | N | 0.214 | 0.151 | 0.0401082797425 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs74607159 |
None | 0.015 | N | 0.214 | 0.151 | 0.0401082797425 | gnomAD-4.0.0 | 6.57142E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47011E-05 | 0 | 0 |
| D/G | rs1422502789 |
0.061 | 0.822 | N | 0.402 | 0.464 | 0.27132560031 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs770418360 |
0.467 | 0.025 | N | 0.205 | 0.219 | 0.226586394389 | gnomAD-2.1.1 | 7.24E-05 | None | None | None | None | I | None | 0 | 5.22193E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs770418360 |
0.467 | 0.025 | N | 0.205 | 0.219 | 0.226586394389 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 1.96464E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs770418360 |
0.467 | 0.025 | N | 0.205 | 0.219 | 0.226586394389 | gnomAD-4.0.0 | 2.94992E-05 | None | None | None | None | I | None | 0 | 3.9028E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1638 | likely_benign | 0.1788 | benign | 0.074 | Stabilizing | 0.822 | D | 0.465 | neutral | N | 0.472577145 | None | None | I |
| D/C | 0.6889 | likely_pathogenic | 0.7318 | pathogenic | 0.028 | Stabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | I |
| D/E | 0.1345 | likely_benign | 0.148 | benign | -0.355 | Destabilizing | 0.015 | N | 0.214 | neutral | N | 0.447942174 | None | None | I |
| D/F | 0.6642 | likely_pathogenic | 0.6925 | pathogenic | -0.127 | Destabilizing | 0.993 | D | 0.574 | neutral | None | None | None | None | I |
| D/G | 0.1914 | likely_benign | 0.2045 | benign | -0.014 | Destabilizing | 0.822 | D | 0.402 | neutral | N | 0.494968389 | None | None | I |
| D/H | 0.3422 | ambiguous | 0.3615 | ambiguous | 0.398 | Stabilizing | 0.97 | D | 0.47 | neutral | N | 0.500115887 | None | None | I |
| D/I | 0.3896 | ambiguous | 0.3974 | ambiguous | 0.231 | Stabilizing | 0.978 | D | 0.566 | neutral | None | None | None | None | I |
| D/K | 0.4264 | ambiguous | 0.4299 | ambiguous | 0.515 | Stabilizing | 0.754 | D | 0.428 | neutral | None | None | None | None | I |
| D/L | 0.4326 | ambiguous | 0.4627 | ambiguous | 0.231 | Stabilizing | 0.956 | D | 0.52 | neutral | None | None | None | None | I |
| D/M | 0.6218 | likely_pathogenic | 0.6589 | pathogenic | 0.116 | Stabilizing | 0.998 | D | 0.586 | neutral | None | None | None | None | I |
| D/N | 0.1261 | likely_benign | 0.1244 | benign | 0.365 | Stabilizing | 0.025 | N | 0.205 | neutral | N | 0.508609264 | None | None | I |
| D/P | 0.6442 | likely_pathogenic | 0.6782 | pathogenic | 0.196 | Stabilizing | 0.978 | D | 0.46 | neutral | None | None | None | None | I |
| D/Q | 0.3927 | ambiguous | 0.4079 | ambiguous | 0.344 | Stabilizing | 0.915 | D | 0.384 | neutral | None | None | None | None | I |
| D/R | 0.472 | ambiguous | 0.4671 | ambiguous | 0.638 | Stabilizing | 0.956 | D | 0.493 | neutral | None | None | None | None | I |
| D/S | 0.1305 | likely_benign | 0.1355 | benign | 0.279 | Stabilizing | 0.86 | D | 0.398 | neutral | None | None | None | None | I |
| D/T | 0.2546 | likely_benign | 0.2726 | benign | 0.351 | Stabilizing | 0.86 | D | 0.457 | neutral | None | None | None | None | I |
| D/V | 0.2251 | likely_benign | 0.2284 | benign | 0.196 | Stabilizing | 0.97 | D | 0.522 | neutral | N | 0.506245323 | None | None | I |
| D/W | 0.9065 | likely_pathogenic | 0.9218 | pathogenic | -0.129 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | I |
| D/Y | 0.3128 | likely_benign | 0.3259 | benign | 0.088 | Stabilizing | 0.99 | D | 0.569 | neutral | N | 0.508787567 | 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.