Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1494 | 4705;4706;4707 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| N2AB | 1494 | 4705;4706;4707 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| N2A | 1494 | 4705;4706;4707 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| N2B | 1448 | 4567;4568;4569 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| Novex-1 | 1448 | 4567;4568;4569 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| Novex-2 | 1448 | 4567;4568;4569 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
| Novex-3 | 1494 | 4705;4706;4707 | chr2:178777704;178777584;178777583 | chr2:179642431;179642311;179642310 |
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/C | rs774506028  |
-0.536 | 1.0 | D | 0.726 | 0.875 | 0.923634717864 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 4.62E-05 | 8.83E-06 | 0 |
| G/C | rs774506028 |
-0.536 | 1.0 | D | 0.726 | 0.875 | 0.923634717864 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31932E-05 | 0 |
| G/S | rs774506028 |
-0.203 | 1.0 | D | 0.672 | 0.776 | 0.626919690049 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| G/S | rs774506028 |
-0.203 | 1.0 | D | 0.672 | 0.776 | 0.626919690049 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| G/S | rs774506028 |
-0.203 | 1.0 | D | 0.672 | 0.776 | 0.626919690049 | gnomAD-4.0.0 | 2.47856E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.38999E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5593 | ambiguous | 0.5075 | ambiguous | -0.439 | Destabilizing | 1.0 | D | 0.572 | neutral | D | 0.700507959 | None | None | I |
| G/C | 0.6682 | likely_pathogenic | 0.6237 | pathogenic | -0.898 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | D | 0.8129843 | None | None | I |
| G/D | 0.3881 | ambiguous | 0.347 | ambiguous | -0.659 | Destabilizing | 1.0 | D | 0.625 | neutral | D | 0.592314931 | None | None | I |
| G/E | 0.5155 | ambiguous | 0.4653 | ambiguous | -0.799 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| G/F | 0.9573 | likely_pathogenic | 0.9473 | pathogenic | -1.018 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| G/H | 0.617 | likely_pathogenic | 0.5796 | pathogenic | -0.672 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| G/I | 0.9294 | likely_pathogenic | 0.9055 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| G/K | 0.5663 | likely_pathogenic | 0.532 | ambiguous | -0.995 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| G/L | 0.924 | likely_pathogenic | 0.9046 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| G/M | 0.9144 | likely_pathogenic | 0.896 | pathogenic | -0.529 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| G/N | 0.3754 | ambiguous | 0.3394 | benign | -0.645 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| G/P | 0.9969 | likely_pathogenic | 0.9963 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| G/Q | 0.4937 | ambiguous | 0.4579 | ambiguous | -0.906 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| G/R | 0.4641 | ambiguous | 0.4271 | ambiguous | -0.526 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.706812539 | None | None | I |
| G/S | 0.1876 | likely_benign | 0.1622 | benign | -0.814 | Destabilizing | 1.0 | D | 0.672 | neutral | D | 0.646360582 | None | None | I |
| G/T | 0.6623 | likely_pathogenic | 0.6153 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| G/V | 0.8872 | likely_pathogenic | 0.8525 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | D | 0.743050143 | None | None | I |
| G/W | 0.9087 | likely_pathogenic | 0.8944 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| G/Y | 0.8843 | likely_pathogenic | 0.8583 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | 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.