Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24852 | 74779;74780;74781 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| N2AB | 23211 | 69856;69857;69858 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| N2A | 22284 | 67075;67076;67077 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| N2B | 15787 | 47584;47585;47586 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| Novex-1 | 15912 | 47959;47960;47961 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| Novex-2 | 15979 | 48160;48161;48162 | chr2:178571578;178571577;178571576 | chr2:179436305;179436304;179436303 |
| 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/A | None | None | 0.773 | N | 0.437 | 0.196 | 0.214338557667 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/Y | rs375466935  |
-0.678 | 0.994 | N | 0.513 | 0.462 | None | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 2.29463E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/Y | rs375466935 |
-0.678 | 0.994 | N | 0.513 | 0.462 | None | 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 |
| S/Y | rs375466935 |
-0.678 | 0.994 | N | 0.513 | 0.462 | None | gnomAD-4.0.0 | 3.8464E-06 | None | None | None | None | N | None | 3.38478E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39425E-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 | 0.0997 | likely_benign | 0.0968 | benign | -0.229 | Destabilizing | 0.773 | D | 0.437 | neutral | N | 0.483656939 | None | None | N |
| S/C | 0.193 | likely_benign | 0.1765 | benign | -0.381 | Destabilizing | 0.999 | D | 0.469 | neutral | N | 0.492070387 | None | None | N |
| S/D | 0.6569 | likely_pathogenic | 0.61 | pathogenic | -0.106 | Destabilizing | 0.957 | D | 0.361 | neutral | None | None | None | None | N |
| S/E | 0.7656 | likely_pathogenic | 0.7244 | pathogenic | -0.218 | Destabilizing | 0.916 | D | 0.393 | neutral | None | None | None | None | N |
| S/F | 0.5446 | ambiguous | 0.4638 | ambiguous | -1.001 | Destabilizing | 0.994 | D | 0.51 | neutral | N | 0.501415981 | None | None | N |
| S/G | 0.1225 | likely_benign | 0.1128 | benign | -0.245 | Destabilizing | 0.916 | D | 0.395 | neutral | None | None | None | None | N |
| S/H | 0.6387 | likely_pathogenic | 0.5906 | pathogenic | -0.58 | Destabilizing | 0.997 | D | 0.429 | neutral | None | None | None | None | N |
| S/I | 0.4647 | ambiguous | 0.4174 | ambiguous | -0.314 | Destabilizing | 0.987 | D | 0.511 | neutral | None | None | None | None | N |
| S/K | 0.8832 | likely_pathogenic | 0.8551 | pathogenic | -0.385 | Destabilizing | 0.845 | D | 0.395 | neutral | None | None | None | None | N |
| S/L | 0.1789 | likely_benign | 0.1566 | benign | -0.314 | Destabilizing | 0.916 | D | 0.403 | neutral | None | None | None | None | N |
| S/M | 0.3155 | likely_benign | 0.2779 | benign | -0.18 | Destabilizing | 0.999 | D | 0.433 | neutral | None | None | None | None | N |
| S/N | 0.236 | likely_benign | 0.2142 | benign | -0.18 | Destabilizing | 0.916 | D | 0.38 | neutral | None | None | None | None | N |
| S/P | 0.8209 | likely_pathogenic | 0.829 | pathogenic | -0.265 | Destabilizing | 0.994 | D | 0.445 | neutral | N | 0.504109569 | None | None | N |
| S/Q | 0.7145 | likely_pathogenic | 0.6736 | pathogenic | -0.409 | Destabilizing | 0.975 | D | 0.399 | neutral | None | None | None | None | N |
| S/R | 0.8604 | likely_pathogenic | 0.8273 | pathogenic | -0.158 | Destabilizing | 0.073 | N | 0.307 | neutral | None | None | None | None | N |
| S/T | 0.0836 | likely_benign | 0.0784 | benign | -0.296 | Destabilizing | 0.892 | D | 0.414 | neutral | N | 0.426398147 | None | None | N |
| S/V | 0.3743 | ambiguous | 0.3358 | benign | -0.265 | Destabilizing | 0.987 | D | 0.484 | neutral | None | None | None | None | N |
| S/W | 0.7379 | likely_pathogenic | 0.6775 | pathogenic | -1.084 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| S/Y | 0.4678 | ambiguous | 0.4114 | ambiguous | -0.777 | Destabilizing | 0.994 | D | 0.513 | neutral | N | 0.485233532 | 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.