Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19904 | 59935;59936;59937 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| N2AB | 18263 | 55012;55013;55014 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| N2A | 17336 | 52231;52232;52233 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| N2B | 10839 | 32740;32741;32742 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| Novex-1 | 10964 | 33115;33116;33117 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| Novex-2 | 11031 | 33316;33317;33318 | chr2:178592194;178592193;178592192 | chr2:179456921;179456920;179456919 |
| 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 | rs1016296280  |
None | 0.454 | N | 0.442 | 0.427 | 0.339074221408 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs1016296280 |
None | 0.454 | N | 0.442 | 0.427 | 0.339074221408 | gnomAD-4.0.0 | 2.03046E-06 | None | None | None | None | N | None | 3.49601E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs762301068 |
-0.219 | 0.005 | N | 0.091 | 0.16 | 0.241664281697 | gnomAD-2.1.1 | 8.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/N | rs762301068 |
-0.219 | 0.005 | N | 0.091 | 0.16 | 0.241664281697 | 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 | rs762301068 |
-0.219 | 0.005 | N | 0.091 | 0.16 | 0.241664281697 | gnomAD-4.0.0 | 8.68416E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18735E-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 | 0.6906 | likely_pathogenic | 0.7863 | pathogenic | -0.326 | Destabilizing | 0.669 | D | 0.525 | neutral | N | 0.472320291 | None | None | N |
| D/C | 0.9241 | likely_pathogenic | 0.9473 | pathogenic | 0.105 | Stabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| D/E | 0.7088 | likely_pathogenic | 0.7569 | pathogenic | -0.683 | Destabilizing | 0.625 | D | 0.374 | neutral | N | 0.470154244 | None | None | N |
| D/F | 0.9527 | likely_pathogenic | 0.966 | pathogenic | -0.563 | Destabilizing | 0.991 | D | 0.635 | neutral | None | None | None | None | N |
| D/G | 0.6498 | likely_pathogenic | 0.7774 | pathogenic | -0.581 | Destabilizing | 0.454 | N | 0.442 | neutral | N | 0.489641305 | None | None | N |
| D/H | 0.7203 | likely_pathogenic | 0.8315 | pathogenic | -0.916 | Destabilizing | 0.966 | D | 0.549 | neutral | N | 0.488880836 | None | None | N |
| D/I | 0.9084 | likely_pathogenic | 0.9431 | pathogenic | 0.313 | Stabilizing | 0.974 | D | 0.635 | neutral | None | None | None | None | N |
| D/K | 0.9004 | likely_pathogenic | 0.9414 | pathogenic | 0.066 | Stabilizing | 0.842 | D | 0.413 | neutral | None | None | None | None | N |
| D/L | 0.9083 | likely_pathogenic | 0.9358 | pathogenic | 0.313 | Stabilizing | 0.974 | D | 0.567 | neutral | None | None | None | None | N |
| D/M | 0.9547 | likely_pathogenic | 0.9718 | pathogenic | 0.783 | Stabilizing | 0.998 | D | 0.628 | neutral | None | None | None | None | N |
| D/N | 0.1329 | likely_benign | 0.2321 | benign | -0.225 | Destabilizing | 0.005 | N | 0.091 | neutral | N | 0.42607286 | None | None | N |
| D/P | 0.9596 | likely_pathogenic | 0.9677 | pathogenic | 0.124 | Stabilizing | 0.974 | D | 0.525 | neutral | None | None | None | None | N |
| D/Q | 0.8747 | likely_pathogenic | 0.9267 | pathogenic | -0.167 | Destabilizing | 0.974 | D | 0.465 | neutral | None | None | None | None | N |
| D/R | 0.8965 | likely_pathogenic | 0.9394 | pathogenic | -0.038 | Destabilizing | 0.949 | D | 0.55 | neutral | None | None | None | None | N |
| D/S | 0.3332 | likely_benign | 0.4785 | ambiguous | -0.373 | Destabilizing | 0.172 | N | 0.125 | neutral | None | None | None | None | N |
| D/T | 0.648 | likely_pathogenic | 0.7762 | pathogenic | -0.164 | Destabilizing | 0.728 | D | 0.438 | neutral | None | None | None | None | N |
| D/V | 0.8202 | likely_pathogenic | 0.8825 | pathogenic | 0.124 | Stabilizing | 0.966 | D | 0.587 | neutral | N | 0.496767648 | None | None | N |
| D/W | 0.9887 | likely_pathogenic | 0.9922 | pathogenic | -0.554 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/Y | 0.7084 | likely_pathogenic | 0.8046 | pathogenic | -0.35 | Destabilizing | 0.989 | D | 0.635 | neutral | N | 0.516139351 | 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.