Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25306 | 76141;76142;76143 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| N2AB | 23665 | 71218;71219;71220 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| N2A | 22738 | 68437;68438;68439 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| N2B | 16241 | 48946;48947;48948 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| Novex-1 | 16366 | 49321;49322;49323 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| Novex-2 | 16433 | 49522;49523;49524 | chr2:178570216;178570215;178570214 | chr2:179434943;179434942;179434941 |
| 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/G | None | None | 0.166 | N | 0.519 | 0.132 | 0.191931220699 | gnomAD-4.0.0 | 1.59196E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8593E-06 | 0 | 0 |
| D/H | None | None | 0.007 | N | 0.467 | 0.313 | 0.269111216191 | gnomAD-4.0.0 | 1.36868E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.82848E-05 | 0 | None | 0 | 0 | 0 | 0 | 1.65706E-05 |
| D/N | rs1447695905  |
None | 0.013 | N | 0.411 | 0.264 | 0.28058544554 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1447695905 |
None | 0.013 | N | 0.411 | 0.264 | 0.28058544554 | gnomAD-4.0.0 | 6.57825E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47093E-05 | 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 | 0.068 | likely_benign | 0.0929 | benign | -0.251 | Destabilizing | 0.001 | N | 0.507 | neutral | N | 0.4963988 | None | None | N |
| D/C | 0.3089 | likely_benign | 0.4629 | ambiguous | 0.124 | Stabilizing | 0.972 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/E | 0.1038 | likely_benign | 0.1532 | benign | -0.633 | Destabilizing | 0.013 | N | 0.359 | neutral | N | 0.501973341 | None | None | N |
| D/F | 0.3799 | ambiguous | 0.5464 | ambiguous | -0.356 | Destabilizing | 0.818 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/G | 0.0878 | likely_benign | 0.1005 | benign | -0.516 | Destabilizing | 0.166 | N | 0.519 | neutral | N | 0.430515887 | None | None | N |
| D/H | 0.1906 | likely_benign | 0.2631 | benign | -0.67 | Destabilizing | 0.007 | N | 0.467 | neutral | N | 0.510036511 | None | None | N |
| D/I | 0.2263 | likely_benign | 0.3728 | ambiguous | 0.411 | Stabilizing | 0.39 | N | 0.667 | neutral | None | None | None | None | N |
| D/K | 0.2492 | likely_benign | 0.3519 | ambiguous | 0.071 | Stabilizing | 0.209 | N | 0.511 | neutral | None | None | None | None | N |
| D/L | 0.1582 | likely_benign | 0.2678 | benign | 0.411 | Stabilizing | 0.004 | N | 0.563 | neutral | None | None | None | None | N |
| D/M | 0.3001 | likely_benign | 0.4879 | ambiguous | 0.779 | Stabilizing | 0.818 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/N | 0.0823 | likely_benign | 0.0982 | benign | -0.182 | Destabilizing | 0.013 | N | 0.411 | neutral | N | 0.491082882 | None | None | N |
| D/P | 0.6456 | likely_pathogenic | 0.7418 | pathogenic | 0.215 | Stabilizing | 0.722 | D | 0.593 | neutral | None | None | None | None | N |
| D/Q | 0.2048 | likely_benign | 0.3019 | benign | -0.132 | Destabilizing | 0.017 | N | 0.39 | neutral | None | None | None | None | N |
| D/R | 0.2947 | likely_benign | 0.4081 | ambiguous | 0.054 | Stabilizing | 0.39 | N | 0.652 | neutral | None | None | None | None | N |
| D/S | 0.0695 | likely_benign | 0.081 | benign | -0.343 | Destabilizing | 0.047 | N | 0.379 | neutral | None | None | None | None | N |
| D/T | 0.1113 | likely_benign | 0.1569 | benign | -0.139 | Destabilizing | 0.209 | N | 0.517 | neutral | None | None | None | None | N |
| D/V | 0.1284 | likely_benign | 0.1982 | benign | 0.215 | Stabilizing | 0.003 | N | 0.566 | neutral | N | 0.498173227 | None | None | N |
| D/W | 0.7772 | likely_pathogenic | 0.8835 | pathogenic | -0.319 | Destabilizing | 0.991 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/Y | 0.1731 | likely_benign | 0.239 | benign | -0.137 | Destabilizing | 0.772 | D | 0.692 | prob.neutral | N | 0.491843351 | 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.