Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29978 | 90157;90158;90159 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| N2AB | 28337 | 85234;85235;85236 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| N2A | 27410 | 82453;82454;82455 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| N2B | 20913 | 62962;62963;62964 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| Novex-1 | 21038 | 63337;63338;63339 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| Novex-2 | 21105 | 63538;63539;63540 | chr2:178552968;178552967;178552966 | chr2:179417695;179417694;179417693 |
| 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 | rs746391024  |
-0.194 | 0.98 | N | 0.492 | 0.413 | 0.266385636622 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/G | rs746391024 |
-0.194 | 0.98 | N | 0.492 | 0.413 | 0.266385636622 | gnomAD-4.0.0 | 6.84609E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99459E-07 | 0 | 0 |
| R/K | rs570797774 |
None | 0.122 | N | 0.2 | 0.136 | 0.186928172975 | gnomAD-4.0.0 | 1.36925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79892E-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 | 0.7886 | likely_pathogenic | 0.6898 | pathogenic | -0.026 | Destabilizing | 0.931 | D | 0.477 | neutral | None | None | None | None | N |
| R/C | 0.4467 | ambiguous | 0.3108 | benign | -0.328 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | N |
| R/D | 0.9196 | likely_pathogenic | 0.8703 | pathogenic | -0.373 | Destabilizing | 0.996 | D | 0.497 | neutral | None | None | None | None | N |
| R/E | 0.7546 | likely_pathogenic | 0.6725 | pathogenic | -0.343 | Destabilizing | 0.97 | D | 0.509 | neutral | None | None | None | None | N |
| R/F | 0.8693 | likely_pathogenic | 0.7978 | pathogenic | -0.363 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| R/G | 0.6045 | likely_pathogenic | 0.4558 | ambiguous | -0.145 | Destabilizing | 0.98 | D | 0.492 | neutral | N | 0.442439461 | None | None | N |
| R/H | 0.2471 | likely_benign | 0.1811 | benign | -0.593 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| R/I | 0.6169 | likely_pathogenic | 0.5272 | ambiguous | 0.241 | Stabilizing | 0.998 | D | 0.581 | neutral | N | 0.504530857 | None | None | N |
| R/K | 0.1455 | likely_benign | 0.1192 | benign | -0.264 | Destabilizing | 0.122 | N | 0.2 | neutral | N | 0.369792716 | None | None | N |
| R/L | 0.542 | ambiguous | 0.4607 | ambiguous | 0.241 | Stabilizing | 0.985 | D | 0.492 | neutral | None | None | None | None | N |
| R/M | 0.5591 | ambiguous | 0.4536 | ambiguous | -0.15 | Destabilizing | 1.0 | D | 0.576 | neutral | None | None | None | None | N |
| R/N | 0.8461 | likely_pathogenic | 0.7735 | pathogenic | -0.181 | Destabilizing | 0.985 | D | 0.511 | neutral | None | None | None | None | N |
| R/P | 0.842 | likely_pathogenic | 0.7408 | pathogenic | 0.169 | Stabilizing | 0.999 | D | 0.555 | neutral | None | None | None | None | N |
| R/Q | 0.2293 | likely_benign | 0.1712 | benign | -0.217 | Destabilizing | 0.97 | D | 0.51 | neutral | None | None | None | None | N |
| R/S | 0.8786 | likely_pathogenic | 0.8075 | pathogenic | -0.341 | Destabilizing | 0.961 | D | 0.502 | neutral | N | 0.465876468 | None | None | N |
| R/T | 0.7135 | likely_pathogenic | 0.5886 | pathogenic | -0.216 | Destabilizing | 0.98 | D | 0.522 | neutral | N | 0.471533004 | None | None | N |
| R/V | 0.7167 | likely_pathogenic | 0.6227 | pathogenic | 0.169 | Stabilizing | 0.996 | D | 0.531 | neutral | None | None | None | None | N |
| R/W | 0.4667 | ambiguous | 0.3457 | ambiguous | -0.558 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| R/Y | 0.6766 | likely_pathogenic | 0.5498 | ambiguous | -0.168 | Destabilizing | 0.999 | D | 0.573 | 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.