Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23754 | 71485;71486;71487 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| N2AB | 22113 | 66562;66563;66564 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| N2A | 21186 | 63781;63782;63783 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| N2B | 14689 | 44290;44291;44292 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| Novex-1 | 14814 | 44665;44666;44667 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| Novex-2 | 14881 | 44866;44867;44868 | chr2:178574872;178574871;178574870 | chr2:179439599;179439598;179439597 |
| 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/H | rs985842925  |
-0.774 | 1.0 | N | 0.631 | 0.438 | 0.316198179892 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| D/H | rs985842925 |
-0.774 | 1.0 | N | 0.631 | 0.438 | 0.316198179892 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/H | rs985842925 |
-0.774 | 1.0 | N | 0.631 | 0.438 | 0.316198179892 | gnomAD-4.0.0 | 2.4801E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39122E-06 | 0 | 0 |
| D/N | rs985842925 |
-0.709 | 1.0 | N | 0.684 | 0.377 | 0.299427821978 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| D/N | rs985842925 |
-0.709 | 1.0 | N | 0.684 | 0.377 | 0.299427821978 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs985842925 |
-0.709 | 1.0 | N | 0.684 | 0.377 | 0.299427821978 | gnomAD-4.0.0 | 1.79807E-05 | None | None | None | None | I | None | 1.20186E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52605E-05 | 1.09832E-05 | 1.60226E-05 |
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 | 0.8151 | likely_pathogenic | 0.7158 | pathogenic | -0.386 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.468041103 | None | None | I |
| D/C | 0.9672 | likely_pathogenic | 0.9511 | pathogenic | -0.082 | Destabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | I |
| D/E | 0.8063 | likely_pathogenic | 0.7101 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.445 | neutral | N | 0.483979311 | None | None | I |
| D/F | 0.9788 | likely_pathogenic | 0.9608 | pathogenic | -0.482 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | I |
| D/G | 0.7727 | likely_pathogenic | 0.6844 | pathogenic | -0.683 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.498858016 | None | None | I |
| D/H | 0.8886 | likely_pathogenic | 0.8177 | pathogenic | -0.915 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.482297471 | None | None | I |
| D/I | 0.9321 | likely_pathogenic | 0.8881 | pathogenic | 0.373 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/K | 0.9382 | likely_pathogenic | 0.9055 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/L | 0.9223 | likely_pathogenic | 0.8823 | pathogenic | 0.373 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/M | 0.9647 | likely_pathogenic | 0.9414 | pathogenic | 0.832 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| D/N | 0.1945 | likely_benign | 0.1611 | benign | -0.575 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.513345128 | None | None | I |
| D/P | 0.9723 | likely_pathogenic | 0.9512 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/Q | 0.9251 | likely_pathogenic | 0.8798 | pathogenic | -0.476 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/R | 0.9463 | likely_pathogenic | 0.9172 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/S | 0.4362 | ambiguous | 0.3528 | ambiguous | -0.773 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/T | 0.5737 | likely_pathogenic | 0.4568 | ambiguous | -0.537 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| D/V | 0.8453 | likely_pathogenic | 0.7726 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.502363509 | None | None | I |
| D/W | 0.9966 | likely_pathogenic | 0.9937 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| D/Y | 0.8625 | likely_pathogenic | 0.7808 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.521735211 | 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.