Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20929 | 63010;63011;63012 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| N2AB | 19288 | 58087;58088;58089 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| N2A | 18361 | 55306;55307;55308 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| N2B | 11864 | 35815;35816;35817 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| Novex-1 | 11989 | 36190;36191;36192 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| Novex-2 | 12056 | 36391;36392;36393 | chr2:178588940;178588939;178588938 | chr2:179453667;179453666;179453665 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs794729471  |
-0.701 | 0.961 | N | 0.485 | 0.301 | 0.573582730237 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/T | rs794729471 |
-0.701 | 0.961 | N | 0.485 | 0.301 | 0.573582730237 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs794729471 |
-0.701 | 0.961 | N | 0.485 | 0.301 | 0.573582730237 | gnomAD-4.0.0 | 3.72063E-06 | None | None | None | None | N | None | 2.67187E-05 | 0 | None | 3.37929E-05 | 0 | None | 0 | 0 | 2.54361E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5877 | likely_pathogenic | 0.7374 | pathogenic | -1.264 | Destabilizing | 0.931 | D | 0.513 | neutral | None | None | None | None | N |
| I/C | 0.9163 | likely_pathogenic | 0.9522 | pathogenic | -0.792 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | N |
| I/D | 0.9775 | likely_pathogenic | 0.9918 | pathogenic | -0.438 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| I/E | 0.9172 | likely_pathogenic | 0.9622 | pathogenic | -0.466 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| I/F | 0.4842 | ambiguous | 0.6159 | pathogenic | -0.917 | Destabilizing | 0.996 | D | 0.466 | neutral | None | None | None | None | N |
| I/G | 0.919 | likely_pathogenic | 0.9642 | pathogenic | -1.539 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| I/H | 0.8712 | likely_pathogenic | 0.9395 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| I/K | 0.8206 | likely_pathogenic | 0.9063 | pathogenic | -0.693 | Destabilizing | 0.998 | D | 0.642 | neutral | N | 0.458833065 | None | None | N |
| I/L | 0.1524 | likely_benign | 0.1911 | benign | -0.611 | Destabilizing | 0.689 | D | 0.233 | neutral | N | 0.466049826 | None | None | N |
| I/M | 0.1715 | likely_benign | 0.2199 | benign | -0.524 | Destabilizing | 0.994 | D | 0.503 | neutral | N | 0.521481822 | None | None | N |
| I/N | 0.7907 | likely_pathogenic | 0.9006 | pathogenic | -0.489 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| I/P | 0.9379 | likely_pathogenic | 0.9585 | pathogenic | -0.795 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| I/Q | 0.7655 | likely_pathogenic | 0.8745 | pathogenic | -0.678 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| I/R | 0.6971 | likely_pathogenic | 0.8319 | pathogenic | -0.094 | Destabilizing | 0.998 | D | 0.649 | neutral | N | 0.479208338 | None | None | N |
| I/S | 0.6841 | likely_pathogenic | 0.8315 | pathogenic | -1.104 | Destabilizing | 0.996 | D | 0.52 | neutral | None | None | None | None | N |
| I/T | 0.3526 | ambiguous | 0.5057 | ambiguous | -1.009 | Destabilizing | 0.961 | D | 0.485 | neutral | N | 0.45889178 | None | None | N |
| I/V | 0.1663 | likely_benign | 0.2436 | benign | -0.795 | Destabilizing | 0.122 | N | 0.131 | neutral | N | 0.419528103 | None | None | N |
| I/W | 0.9033 | likely_pathogenic | 0.9408 | pathogenic | -0.921 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8427 | likely_pathogenic | 0.9116 | pathogenic | -0.699 | Destabilizing | 0.999 | D | 0.566 | 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.