Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20753 | 62482;62483;62484 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| N2AB | 19112 | 57559;57560;57561 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| N2A | 18185 | 54778;54779;54780 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| N2B | 11688 | 35287;35288;35289 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| Novex-1 | 11813 | 35662;35663;35664 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| Novex-2 | 11880 | 35863;35864;35865 | chr2:178589468;178589467;178589466 | chr2:179454195;179454194;179454193 |
| 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 | None | None | 0.78 | N | 0.467 | 0.115 | 0.226586394389 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs879217628  |
None | 0.026 | N | 0.251 | 0.144 | None | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85905E-06 | 0 | 0 |
| D/V | None | None | 0.896 | N | 0.668 | 0.222 | 0.351830644314 | gnomAD-4.0.0 | 1.59207E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 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 | 0.1317 | likely_benign | 0.1411 | benign | -0.546 | Destabilizing | 0.046 | N | 0.305 | neutral | N | 0.441615529 | None | None | N |
| D/C | 0.5638 | ambiguous | 0.6022 | pathogenic | -0.159 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/E | 0.1287 | likely_benign | 0.1369 | benign | -0.559 | Destabilizing | 0.78 | D | 0.467 | neutral | N | 0.394957732 | None | None | N |
| D/F | 0.5384 | ambiguous | 0.5855 | pathogenic | -0.338 | Destabilizing | 0.996 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/G | 0.1683 | likely_benign | 0.18 | benign | -0.8 | Destabilizing | 0.64 | D | 0.541 | neutral | N | 0.472514439 | None | None | N |
| D/H | 0.2873 | likely_benign | 0.3001 | benign | -0.375 | Destabilizing | 0.984 | D | 0.655 | neutral | N | 0.455142186 | None | None | N |
| D/I | 0.3252 | likely_benign | 0.371 | ambiguous | 0.097 | Stabilizing | 0.988 | D | 0.675 | neutral | None | None | None | None | N |
| D/K | 0.3128 | likely_benign | 0.326 | benign | -0.107 | Destabilizing | 0.919 | D | 0.651 | neutral | None | None | None | None | N |
| D/L | 0.286 | likely_benign | 0.3186 | benign | 0.097 | Stabilizing | 0.919 | D | 0.664 | neutral | None | None | None | None | N |
| D/M | 0.5124 | ambiguous | 0.5669 | pathogenic | 0.374 | Stabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/N | 0.0812 | likely_benign | 0.091 | benign | -0.424 | Destabilizing | 0.026 | N | 0.251 | neutral | N | 0.458009133 | None | None | N |
| D/P | 0.4727 | ambiguous | 0.4334 | ambiguous | -0.094 | Destabilizing | 0.988 | D | 0.653 | neutral | None | None | None | None | N |
| D/Q | 0.2785 | likely_benign | 0.2928 | benign | -0.374 | Destabilizing | 0.988 | D | 0.576 | neutral | None | None | None | None | N |
| D/R | 0.3628 | ambiguous | 0.3788 | ambiguous | 0.116 | Stabilizing | 0.976 | D | 0.655 | neutral | None | None | None | None | N |
| D/S | 0.1045 | likely_benign | 0.1156 | benign | -0.581 | Destabilizing | 0.702 | D | 0.471 | neutral | None | None | None | None | N |
| D/T | 0.2122 | likely_benign | 0.2323 | benign | -0.384 | Destabilizing | 0.919 | D | 0.577 | neutral | None | None | None | None | N |
| D/V | 0.2084 | likely_benign | 0.2318 | benign | -0.094 | Destabilizing | 0.896 | D | 0.668 | neutral | N | 0.498239602 | None | None | N |
| D/W | 0.8591 | likely_pathogenic | 0.8623 | pathogenic | -0.148 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| D/Y | 0.2526 | likely_benign | 0.2857 | benign | -0.099 | Destabilizing | 0.995 | D | 0.716 | prob.delet. | N | 0.498933036 | 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.