Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25245 | 75958;75959;75960 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| N2AB | 23604 | 71035;71036;71037 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| N2A | 22677 | 68254;68255;68256 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| N2B | 16180 | 48763;48764;48765 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| Novex-1 | 16305 | 49138;49139;49140 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| Novex-2 | 16372 | 49339;49340;49341 | chr2:178570399;178570398;178570397 | chr2:179435126;179435125;179435124 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs397517701  |
-1.461 | 0.944 | N | 0.459 | 0.205 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.73E-05 | 0 |
| R/K | rs397517701 |
-1.461 | 0.944 | N | 0.459 | 0.205 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/K | rs397517701 |
-1.461 | 0.944 | N | 0.459 | 0.205 | None | gnomAD-4.0.0 | 1.61187E-05 | None | None | None | None | N | None | 1.33547E-05 | 0 | None | 0 | 0 | None | 0 | 1.64582E-04 | 1.69549E-05 | 3.29417E-05 | 1.60195E-05 |
| R/T | rs397517701 |
-1.706 | 0.892 | N | 0.601 | 0.545 | 0.467585353272 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| R/T | rs397517701 |
-1.706 | 0.892 | N | 0.601 | 0.545 | 0.467585353272 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/T | rs397517701 |
-1.706 | 0.892 | N | 0.601 | 0.545 | 0.467585353272 | gnomAD-4.0.0 | 2.47979E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39097E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9838 | likely_pathogenic | 0.986 | pathogenic | -2.102 | Highly Destabilizing | 0.845 | D | 0.547 | neutral | None | None | None | None | N |
| R/C | 0.6298 | likely_pathogenic | 0.5879 | pathogenic | -1.923 | Destabilizing | 0.073 | N | 0.46 | neutral | None | None | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9988 | pathogenic | -1.038 | Destabilizing | 0.996 | D | 0.771 | deleterious | None | None | None | None | N |
| R/E | 0.9767 | likely_pathogenic | 0.9799 | pathogenic | -0.826 | Destabilizing | 0.985 | D | 0.465 | neutral | None | None | None | None | N |
| R/F | 0.9914 | likely_pathogenic | 0.9935 | pathogenic | -1.315 | Destabilizing | 0.987 | D | 0.821 | deleterious | None | None | None | None | N |
| R/G | 0.9657 | likely_pathogenic | 0.9694 | pathogenic | -2.425 | Highly Destabilizing | 0.944 | D | 0.655 | neutral | N | 0.502389962 | None | None | N |
| R/H | 0.7349 | likely_pathogenic | 0.7328 | pathogenic | -2.311 | Highly Destabilizing | 0.999 | D | 0.516 | neutral | None | None | None | None | N |
| R/I | 0.9793 | likely_pathogenic | 0.9847 | pathogenic | -1.158 | Destabilizing | 0.967 | D | 0.811 | deleterious | N | 0.513492778 | None | None | N |
| R/K | 0.4567 | ambiguous | 0.5021 | ambiguous | -1.35 | Destabilizing | 0.944 | D | 0.459 | neutral | N | 0.465265945 | None | None | N |
| R/L | 0.9443 | likely_pathogenic | 0.9581 | pathogenic | -1.158 | Destabilizing | 0.845 | D | 0.629 | neutral | None | None | None | None | N |
| R/M | 0.9476 | likely_pathogenic | 0.9604 | pathogenic | -1.656 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/N | 0.9934 | likely_pathogenic | 0.9943 | pathogenic | -1.315 | Destabilizing | 0.996 | D | 0.489 | neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -1.463 | Destabilizing | 0.996 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Q | 0.5206 | ambiguous | 0.5118 | ambiguous | -1.169 | Destabilizing | 0.996 | D | 0.499 | neutral | None | None | None | None | N |
| R/S | 0.9928 | likely_pathogenic | 0.9931 | pathogenic | -2.192 | Highly Destabilizing | 0.892 | D | 0.592 | neutral | N | 0.486675109 | None | None | N |
| R/T | 0.9833 | likely_pathogenic | 0.9875 | pathogenic | -1.777 | Destabilizing | 0.892 | D | 0.601 | neutral | N | 0.513239288 | None | None | N |
| R/V | 0.9779 | likely_pathogenic | 0.9823 | pathogenic | -1.463 | Destabilizing | 0.975 | D | 0.741 | deleterious | None | None | None | None | N |
| R/W | 0.9132 | likely_pathogenic | 0.9265 | pathogenic | -0.86 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| R/Y | 0.9747 | likely_pathogenic | 0.9791 | pathogenic | -0.733 | Destabilizing | 0.996 | D | 0.792 | deleterious | 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.