Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21331 | 64216;64217;64218 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| N2AB | 19690 | 59293;59294;59295 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| N2A | 18763 | 56512;56513;56514 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| N2B | 12266 | 37021;37022;37023 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| Novex-1 | 12391 | 37396;37397;37398 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| Novex-2 | 12458 | 37597;37598;37599 | chr2:178587220;178587219;178587218 | chr2:179451947;179451946;179451945 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs756494781  |
None | 0.003 | N | 0.077 | 0.087 | 0.363751660372 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs756494781 |
None | 0.003 | N | 0.077 | 0.087 | 0.363751660372 | gnomAD-4.0.0 | 5.57917E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63052E-06 | 0 | 0 |
| V/G | rs756494781 |
-1.655 | 0.521 | N | 0.388 | 0.297 | 0.589755004127 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/G | rs756494781 |
-1.655 | 0.521 | N | 0.388 | 0.297 | 0.589755004127 | gnomAD-4.0.0 | 2.05318E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99679E-07 | 2.31889E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.253 | likely_benign | 0.208 | benign | -1.143 | Destabilizing | 0.003 | N | 0.077 | neutral | N | 0.49681545 | None | None | N |
| V/C | 0.7251 | likely_pathogenic | 0.7021 | pathogenic | -0.749 | Destabilizing | 0.02 | N | 0.208 | neutral | None | None | None | None | N |
| V/D | 0.6115 | likely_pathogenic | 0.4866 | ambiguous | -0.745 | Destabilizing | 0.939 | D | 0.393 | neutral | N | 0.47357083 | None | None | N |
| V/E | 0.484 | ambiguous | 0.3793 | ambiguous | -0.783 | Destabilizing | 0.742 | D | 0.339 | neutral | None | None | None | None | N |
| V/F | 0.2272 | likely_benign | 0.2005 | benign | -0.985 | Destabilizing | 0.884 | D | 0.385 | neutral | N | 0.486350528 | None | None | N |
| V/G | 0.3054 | likely_benign | 0.2581 | benign | -1.406 | Destabilizing | 0.521 | D | 0.388 | neutral | N | 0.500829345 | None | None | N |
| V/H | 0.6331 | likely_pathogenic | 0.5676 | pathogenic | -0.85 | Destabilizing | 0.996 | D | 0.379 | neutral | None | None | None | None | N |
| V/I | 0.0774 | likely_benign | 0.0781 | benign | -0.546 | Destabilizing | 0.309 | N | 0.281 | neutral | N | 0.46087608 | None | None | N |
| V/K | 0.5838 | likely_pathogenic | 0.4683 | ambiguous | -0.884 | Destabilizing | 0.742 | D | 0.361 | neutral | None | None | None | None | N |
| V/L | 0.1602 | likely_benign | 0.1382 | benign | -0.546 | Destabilizing | 0.134 | N | 0.223 | neutral | N | 0.481653997 | None | None | N |
| V/M | 0.1464 | likely_benign | 0.1461 | benign | -0.421 | Destabilizing | 0.206 | N | 0.192 | neutral | None | None | None | None | N |
| V/N | 0.3204 | likely_benign | 0.2697 | benign | -0.64 | Destabilizing | 0.953 | D | 0.395 | neutral | None | None | None | None | N |
| V/P | 0.745 | likely_pathogenic | 0.619 | pathogenic | -0.708 | Destabilizing | 0.953 | D | 0.371 | neutral | None | None | None | None | N |
| V/Q | 0.3627 | ambiguous | 0.3007 | benign | -0.834 | Destabilizing | 0.953 | D | 0.377 | neutral | None | None | None | None | N |
| V/R | 0.5543 | ambiguous | 0.4236 | ambiguous | -0.332 | Destabilizing | 0.953 | D | 0.397 | neutral | None | None | None | None | N |
| V/S | 0.249 | likely_benign | 0.2075 | benign | -1.136 | Destabilizing | 0.59 | D | 0.351 | neutral | None | None | None | None | N |
| V/T | 0.2185 | likely_benign | 0.1939 | benign | -1.061 | Destabilizing | 0.016 | N | 0.076 | neutral | None | None | None | None | N |
| V/W | 0.8704 | likely_pathogenic | 0.8466 | pathogenic | -1.114 | Destabilizing | 0.996 | D | 0.407 | neutral | None | None | None | None | N |
| V/Y | 0.6082 | likely_pathogenic | 0.5539 | ambiguous | -0.822 | Destabilizing | 0.953 | D | 0.381 | 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.