Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34994 | 105205;105206;105207 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| N2AB | 33353 | 100282;100283;100284 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| N2A | 32426 | 97501;97502;97503 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| N2B | 25929 | 78010;78011;78012 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| Novex-1 | 26054 | 78385;78386;78387 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| Novex-2 | 26121 | 78586;78587;78588 | chr2:178531635;178531634;178531633 | chr2:179396362;179396361;179396360 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs774081159  |
0.064 | 0.994 | N | 0.371 | 0.223 | 0.192905019026 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| S/N | rs774081159 |
0.064 | 0.994 | N | 0.371 | 0.223 | 0.192905019026 | gnomAD-4.0.0 | 3.42073E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.7337E-04 | 3.59759E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1323 | likely_benign | 0.1715 | benign | -0.218 | Destabilizing | 0.98 | D | 0.355 | neutral | None | None | None | None | I |
| S/C | 0.3264 | likely_benign | 0.436 | ambiguous | -0.462 | Destabilizing | 1.0 | D | 0.444 | neutral | N | 0.464379074 | None | None | I |
| S/D | 0.762 | likely_pathogenic | 0.8861 | pathogenic | -0.18 | Destabilizing | 0.996 | D | 0.364 | neutral | None | None | None | None | I |
| S/E | 0.8607 | likely_pathogenic | 0.9379 | pathogenic | -0.289 | Destabilizing | 0.999 | D | 0.356 | neutral | None | None | None | None | I |
| S/F | 0.6257 | likely_pathogenic | 0.805 | pathogenic | -0.992 | Destabilizing | 1.0 | D | 0.435 | neutral | None | None | None | None | I |
| S/G | 0.1799 | likely_benign | 0.2294 | benign | -0.225 | Destabilizing | 0.104 | N | 0.215 | neutral | N | 0.418916735 | None | None | I |
| S/H | 0.7368 | likely_pathogenic | 0.8656 | pathogenic | -0.508 | Destabilizing | 1.0 | D | 0.414 | neutral | None | None | None | None | I |
| S/I | 0.685 | likely_pathogenic | 0.8336 | pathogenic | -0.323 | Destabilizing | 0.999 | D | 0.429 | neutral | N | 0.515680852 | None | None | I |
| S/K | 0.9448 | likely_pathogenic | 0.9825 | pathogenic | -0.435 | Destabilizing | 0.996 | D | 0.365 | neutral | None | None | None | None | I |
| S/L | 0.2702 | likely_benign | 0.4218 | ambiguous | -0.323 | Destabilizing | 1.0 | D | 0.359 | neutral | None | None | None | None | I |
| S/M | 0.4641 | ambiguous | 0.5943 | pathogenic | -0.26 | Destabilizing | 1.0 | D | 0.427 | neutral | None | None | None | None | I |
| S/N | 0.4021 | ambiguous | 0.5645 | pathogenic | -0.229 | Destabilizing | 0.994 | D | 0.371 | neutral | N | 0.461422293 | None | None | I |
| S/P | 0.655 | likely_pathogenic | 0.8279 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.406 | neutral | None | None | None | None | I |
| S/Q | 0.83 | likely_pathogenic | 0.9129 | pathogenic | -0.442 | Destabilizing | 1.0 | D | 0.372 | neutral | None | None | None | None | I |
| S/R | 0.9004 | likely_pathogenic | 0.9678 | pathogenic | -0.201 | Destabilizing | 0.999 | D | 0.394 | neutral | N | 0.499729965 | None | None | I |
| S/T | 0.1947 | likely_benign | 0.2542 | benign | -0.348 | Destabilizing | 0.994 | D | 0.369 | neutral | N | 0.499903323 | None | None | I |
| S/V | 0.5804 | likely_pathogenic | 0.7472 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.423 | neutral | None | None | None | None | I |
| S/W | 0.7558 | likely_pathogenic | 0.8788 | pathogenic | -1.089 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | I |
| S/Y | 0.5637 | ambiguous | 0.7517 | pathogenic | -0.782 | Destabilizing | 1.0 | D | 0.436 | neutral | None | None | None | None | I |
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.