Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19640 | 59143;59144;59145 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| N2AB | 17999 | 54220;54221;54222 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| N2A | 17072 | 51439;51440;51441 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| N2B | 10575 | 31948;31949;31950 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| Novex-1 | 10700 | 32323;32324;32325 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| Novex-2 | 10767 | 32524;32525;32526 | chr2:178593290;178593289;178593288 | chr2:179458017;179458016;179458015 |
| 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/G | rs758745272  |
-1.392 | 0.351 | N | 0.485 | 0.227 | 0.411799315854 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 7.99E-05 | 7.81E-06 | 0 |
| R/G | rs758745272 |
-1.392 | 0.351 | N | 0.485 | 0.227 | 0.411799315854 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88466E-04 | 0 | 0 | 0 | 0 |
| R/G | rs758745272 |
-1.392 | 0.351 | N | 0.485 | 0.227 | 0.411799315854 | gnomAD-4.0.0 | 8.97192E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.84511E-05 | 0 | 2.39407E-06 | 0 | 2.84511E-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 | 0.4329 | ambiguous | 0.4757 | ambiguous | -0.954 | Destabilizing | 0.129 | N | 0.374 | neutral | None | None | None | None | N |
| R/C | 0.2129 | likely_benign | 0.2129 | benign | -0.964 | Destabilizing | 0.983 | D | 0.45 | neutral | None | None | None | None | N |
| R/D | 0.7145 | likely_pathogenic | 0.7559 | pathogenic | -0.053 | Destabilizing | 0.418 | N | 0.538 | neutral | None | None | None | None | N |
| R/E | 0.4337 | ambiguous | 0.469 | ambiguous | 0.113 | Stabilizing | 0.129 | N | 0.398 | neutral | None | None | None | None | N |
| R/F | 0.5304 | ambiguous | 0.5835 | pathogenic | -0.6 | Destabilizing | 0.716 | D | 0.56 | neutral | None | None | None | None | N |
| R/G | 0.4502 | ambiguous | 0.4684 | ambiguous | -1.296 | Destabilizing | 0.351 | N | 0.485 | neutral | N | 0.475078541 | None | None | N |
| R/H | 0.1034 | likely_benign | 0.1073 | benign | -1.512 | Destabilizing | 0.94 | D | 0.499 | neutral | None | None | None | None | N |
| R/I | 0.2253 | likely_benign | 0.2472 | benign | -0.019 | Destabilizing | 0.264 | N | 0.534 | neutral | None | None | None | None | N |
| R/K | 0.112 | likely_benign | 0.1069 | benign | -0.794 | Destabilizing | 0.001 | N | 0.218 | neutral | N | 0.418181308 | None | None | N |
| R/L | 0.2253 | likely_benign | 0.2425 | benign | -0.019 | Destabilizing | 0.001 | N | 0.323 | neutral | None | None | None | None | N |
| R/M | 0.2754 | likely_benign | 0.2934 | benign | -0.504 | Destabilizing | 0.655 | D | 0.505 | neutral | N | 0.479660444 | None | None | N |
| R/N | 0.5807 | likely_pathogenic | 0.6317 | pathogenic | -0.498 | Destabilizing | 0.418 | N | 0.455 | neutral | None | None | None | None | N |
| R/P | 0.5875 | likely_pathogenic | 0.6198 | pathogenic | -0.311 | Destabilizing | 0.836 | D | 0.582 | neutral | None | None | None | None | N |
| R/Q | 0.1273 | likely_benign | 0.1299 | benign | -0.536 | Destabilizing | 0.418 | N | 0.456 | neutral | None | None | None | None | N |
| R/S | 0.5212 | ambiguous | 0.565 | pathogenic | -1.303 | Destabilizing | 0.101 | N | 0.439 | neutral | N | 0.497719527 | None | None | N |
| R/T | 0.2213 | likely_benign | 0.2407 | benign | -0.929 | Destabilizing | 0.002 | N | 0.247 | neutral | N | 0.409460251 | None | None | N |
| R/V | 0.2922 | likely_benign | 0.3224 | benign | -0.311 | Destabilizing | 0.264 | N | 0.475 | neutral | None | None | None | None | N |
| R/W | 0.1859 | likely_benign | 0.2009 | benign | -0.225 | Destabilizing | 0.001 | N | 0.379 | neutral | N | 0.471217427 | None | None | N |
| R/Y | 0.368 | ambiguous | 0.4071 | ambiguous | 0.026 | Stabilizing | 0.716 | D | 0.582 | 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.