Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3193 | 9802;9803;9804 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| N2AB | 3193 | 9802;9803;9804 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| N2A | 3193 | 9802;9803;9804 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| N2B | 3147 | 9664;9665;9666 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| Novex-1 | 3147 | 9664;9665;9666 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| Novex-2 | 3147 | 9664;9665;9666 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
| Novex-3 | 3193 | 9802;9803;9804 | chr2:178766507;178766506;178766505 | chr2:179631234;179631233;179631232 |
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/P | None | None | 1.0 | D | 0.664 | 0.718 | 0.671041724158 | gnomAD-4.0.0 | 6.84089E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99311E-07 | 0 | 0 |
| R/Q | rs1034071730  |
-0.164 | 1.0 | D | 0.684 | 0.551 | 0.467585353272 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.63239E-04 |
| R/Q | rs1034071730 |
-0.164 | 1.0 | D | 0.684 | 0.551 | 0.467585353272 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs1034071730 |
-0.164 | 1.0 | D | 0.684 | 0.551 | 0.467585353272 | gnomAD-4.0.0 | 1.98273E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22886E-05 | None | 0 | 0 | 2.37289E-05 | 0 | 4.80138E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8905 | likely_pathogenic | 0.949 | pathogenic | -0.755 | Destabilizing | 0.999 | D | 0.514 | neutral | None | None | None | None | N |
| R/C | 0.7301 | likely_pathogenic | 0.8692 | pathogenic | -0.555 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/D | 0.8966 | likely_pathogenic | 0.9386 | pathogenic | -0.063 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/E | 0.7167 | likely_pathogenic | 0.8439 | pathogenic | 0.085 | Stabilizing | 0.999 | D | 0.558 | neutral | None | None | None | None | N |
| R/F | 0.9451 | likely_pathogenic | 0.9794 | pathogenic | -0.406 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/G | 0.7165 | likely_pathogenic | 0.8809 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.621492855 | None | None | N |
| R/H | 0.3819 | ambiguous | 0.5731 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/I | 0.7527 | likely_pathogenic | 0.8804 | pathogenic | 0.206 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/K | 0.3345 | likely_benign | 0.4373 | ambiguous | -0.769 | Destabilizing | 0.998 | D | 0.418 | neutral | None | None | None | None | N |
| R/L | 0.7224 | likely_pathogenic | 0.8627 | pathogenic | 0.206 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.622162744 | None | None | N |
| R/M | 0.8121 | likely_pathogenic | 0.9296 | pathogenic | -0.134 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/N | 0.82 | likely_pathogenic | 0.882 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/P | 0.9332 | likely_pathogenic | 0.9614 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.664 | neutral | D | 0.662235248 | None | None | N |
| R/Q | 0.3149 | likely_benign | 0.5006 | ambiguous | -0.318 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.595757563 | None | None | N |
| R/S | 0.8985 | likely_pathogenic | 0.9573 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/T | 0.7736 | likely_pathogenic | 0.9024 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/V | 0.8731 | likely_pathogenic | 0.9359 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/W | 0.6023 | likely_pathogenic | 0.826 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8394 | likely_pathogenic | 0.9251 | pathogenic | 0.216 | Stabilizing | 1.0 | D | 0.693 | 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.