Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22745 | 68458;68459;68460 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| N2AB | 21104 | 63535;63536;63537 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| N2A | 20177 | 60754;60755;60756 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| N2B | 13680 | 41263;41264;41265 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| Novex-1 | 13805 | 41638;41639;41640 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| Novex-2 | 13872 | 41839;41840;41841 | chr2:178578707;178578706;178578705 | chr2:179443434;179443433;179443432 |
| 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 | rs757244505  |
-0.683 | 0.005 | N | 0.296 | 0.059 | 0.32714864917 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.39E-05 | None | 0 | 0 | 0 |
| D/E | rs757244505 |
-0.683 | 0.005 | N | 0.296 | 0.059 | 0.32714864917 | gnomAD-4.0.0 | 1.59935E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.45378E-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 | 0.1556 | likely_benign | 0.13 | benign | -0.434 | Destabilizing | 0.669 | D | 0.543 | neutral | N | 0.513382413 | None | None | N |
| D/C | 0.5994 | likely_pathogenic | 0.5381 | ambiguous | -0.268 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/E | 0.1385 | likely_benign | 0.136 | benign | -0.684 | Destabilizing | 0.005 | N | 0.296 | neutral | N | 0.4505258 | None | None | N |
| D/F | 0.6696 | likely_pathogenic | 0.586 | pathogenic | -0.158 | Destabilizing | 0.991 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/G | 0.1742 | likely_benign | 0.1453 | benign | -0.767 | Destabilizing | 0.005 | N | 0.394 | neutral | N | 0.398731543 | None | None | N |
| D/H | 0.4393 | ambiguous | 0.3759 | ambiguous | -0.598 | Destabilizing | 0.991 | D | 0.622 | neutral | N | 0.479259278 | None | None | N |
| D/I | 0.4834 | ambiguous | 0.4145 | ambiguous | 0.436 | Stabilizing | 0.974 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/K | 0.5803 | likely_pathogenic | 0.5296 | ambiguous | -0.536 | Destabilizing | 0.728 | D | 0.548 | neutral | None | None | None | None | N |
| D/L | 0.4281 | ambiguous | 0.3702 | ambiguous | 0.436 | Stabilizing | 0.949 | D | 0.66 | neutral | None | None | None | None | N |
| D/M | 0.6175 | likely_pathogenic | 0.5453 | ambiguous | 0.768 | Stabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/N | 0.1492 | likely_benign | 0.1236 | benign | -0.816 | Destabilizing | 0.801 | D | 0.451 | neutral | D | 0.525023559 | None | None | N |
| D/P | 0.845 | likely_pathogenic | 0.8129 | pathogenic | 0.171 | Stabilizing | 0.974 | D | 0.565 | neutral | None | None | None | None | N |
| D/Q | 0.4253 | ambiguous | 0.3751 | ambiguous | -0.683 | Destabilizing | 0.904 | D | 0.437 | neutral | None | None | None | None | N |
| D/R | 0.6421 | likely_pathogenic | 0.5748 | pathogenic | -0.419 | Destabilizing | 0.949 | D | 0.641 | neutral | None | None | None | None | N |
| D/S | 0.1258 | likely_benign | 0.1048 | benign | -1.056 | Destabilizing | 0.842 | D | 0.365 | neutral | None | None | None | None | N |
| D/T | 0.2708 | likely_benign | 0.2334 | benign | -0.796 | Destabilizing | 0.842 | D | 0.575 | neutral | None | None | None | None | N |
| D/V | 0.2901 | likely_benign | 0.2387 | benign | 0.171 | Stabilizing | 0.966 | D | 0.657 | neutral | N | 0.514595922 | None | None | N |
| D/W | 0.9286 | likely_pathogenic | 0.8991 | pathogenic | -0.063 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3322 | likely_benign | 0.2774 | benign | 0.038 | Stabilizing | 0.989 | D | 0.694 | prob.neutral | N | 0.479005788 | 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.