Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3005 | 9238;9239;9240 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| N2AB | 3005 | 9238;9239;9240 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| N2A | 3005 | 9238;9239;9240 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| N2B | 2959 | 9100;9101;9102 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| Novex-1 | 2959 | 9100;9101;9102 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| Novex-2 | 2959 | 9100;9101;9102 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
| Novex-3 | 3005 | 9238;9239;9240 | chr2:178768823;178768822;178768821 | chr2:179633550;179633549;179633548 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | None | None | 1.0 | D | 0.584 | 0.566 | 0.338110398507 | gnomAD-4.0.0 | 6.84091E-07 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs2090986560  |
None | 1.0 | D | 0.648 | 0.648 | 0.32580497728 | gnomAD-4.0.0 | 4.78864E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87203E-05 | 0 | 3.59719E-06 | 1.15934E-05 | 1.6559E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.6363 | likely_pathogenic | 0.5976 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.584 | neutral | D | 0.657848487 | None | None | N |
| G/C | 0.813 | likely_pathogenic | 0.79 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.660394614 | None | None | N |
| G/D | 0.5034 | ambiguous | 0.4878 | ambiguous | -0.728 | Destabilizing | 1.0 | D | 0.648 | neutral | D | 0.540053705 | None | None | N |
| G/E | 0.7344 | likely_pathogenic | 0.6932 | pathogenic | -0.884 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| G/F | 0.9828 | likely_pathogenic | 0.98 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| G/H | 0.849 | likely_pathogenic | 0.8383 | pathogenic | -0.481 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| G/I | 0.969 | likely_pathogenic | 0.9598 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| G/K | 0.8411 | likely_pathogenic | 0.8443 | pathogenic | -0.954 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| G/L | 0.9649 | likely_pathogenic | 0.9564 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| G/M | 0.9567 | likely_pathogenic | 0.9507 | pathogenic | -0.609 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| G/N | 0.5196 | ambiguous | 0.4962 | ambiguous | -0.674 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| G/P | 0.9989 | likely_pathogenic | 0.9987 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| G/Q | 0.769 | likely_pathogenic | 0.7491 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| G/R | 0.7362 | likely_pathogenic | 0.7316 | pathogenic | -0.453 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | D | 0.618619723 | None | None | N |
| G/S | 0.293 | likely_benign | 0.2568 | benign | -0.803 | Destabilizing | 1.0 | D | 0.673 | neutral | D | 0.616212666 | None | None | N |
| G/T | 0.7673 | likely_pathogenic | 0.7452 | pathogenic | -0.892 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| G/V | 0.9397 | likely_pathogenic | 0.9255 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.660394614 | None | None | N |
| G/W | 0.9614 | likely_pathogenic | 0.9593 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| G/Y | 0.9493 | likely_pathogenic | 0.947 | pathogenic | -0.828 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | 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.