Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2972 | 9139;9140;9141 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| N2AB | 2972 | 9139;9140;9141 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| N2A | 2972 | 9139;9140;9141 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| N2B | 2926 | 9001;9002;9003 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| Novex-1 | 2926 | 9001;9002;9003 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| Novex-2 | 2926 | 9001;9002;9003 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
| Novex-3 | 2972 | 9139;9140;9141 | chr2:178768922;178768921;178768920 | chr2:179633649;179633648;179633647 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.999 | N | 0.463 | 0.422 | 0.281780670237 | gnomAD-4.0.0 | 2.05265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69793E-06 | 0 | 0 |
| T/I | rs1244469362  |
None | 1.0 | N | 0.71 | 0.538 | 0.453962894745 | gnomAD-4.0.0 | 2.05265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79863E-06 | 1.15937E-05 | 0 |
| T/S | rs2091002766 |
None | 0.999 | N | 0.465 | 0.307 | 0.260249123532 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs2091002766 |
None | 0.999 | N | 0.465 | 0.307 | 0.260249123532 | gnomAD-4.0.0 | 6.57056E-06 | None | None | None | None | N | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2414 | likely_benign | 0.2368 | benign | -0.568 | Destabilizing | 0.999 | D | 0.463 | neutral | N | 0.501674776 | None | None | N |
| T/C | 0.7334 | likely_pathogenic | 0.769 | pathogenic | -0.309 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| T/D | 0.7614 | likely_pathogenic | 0.7755 | pathogenic | 0.018 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/E | 0.6138 | likely_pathogenic | 0.6135 | pathogenic | -0.037 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| T/F | 0.6272 | likely_pathogenic | 0.6449 | pathogenic | -0.927 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/G | 0.6893 | likely_pathogenic | 0.6736 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/H | 0.5343 | ambiguous | 0.5431 | ambiguous | -1.07 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| T/I | 0.3 | likely_benign | 0.3271 | benign | -0.208 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.447903099 | None | None | N |
| T/K | 0.3631 | ambiguous | 0.373 | ambiguous | -0.533 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| T/L | 0.193 | likely_benign | 0.1796 | benign | -0.208 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/M | 0.1335 | likely_benign | 0.1273 | benign | 0.082 | Stabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| T/N | 0.3443 | ambiguous | 0.3493 | ambiguous | -0.361 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | D | 0.569406478 | None | None | N |
| T/P | 0.628 | likely_pathogenic | 0.6222 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | D | 0.569574865 | None | None | N |
| T/Q | 0.4328 | ambiguous | 0.4213 | ambiguous | -0.589 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| T/R | 0.3617 | ambiguous | 0.3678 | ambiguous | -0.246 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/S | 0.2854 | likely_benign | 0.2757 | benign | -0.595 | Destabilizing | 0.999 | D | 0.465 | neutral | N | 0.472653599 | None | None | N |
| T/V | 0.2295 | likely_benign | 0.2406 | benign | -0.297 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| T/W | 0.9044 | likely_pathogenic | 0.9075 | pathogenic | -0.89 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/Y | 0.6733 | likely_pathogenic | 0.7079 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | 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.