Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21772 | 65539;65540;65541 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| N2AB | 20131 | 60616;60617;60618 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| N2A | 19204 | 57835;57836;57837 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| N2B | 12707 | 38344;38345;38346 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| Novex-1 | 12832 | 38719;38720;38721 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| Novex-2 | 12899 | 38920;38921;38922 | chr2:178583868;178583867;178583866 | chr2:179448595;179448594;179448593 |
| 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/I | None | None | None | N | 0.31 | 0.227 | 0.117506650769 | gnomAD-4.0.0 | 6.90467E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.18675E-05 | 0 |
| S/N | rs768613983  |
-0.388 | None | N | 0.064 | 0.129 | 0.0401082797425 | gnomAD-2.1.1 | 8.5E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.52E-05 | None | 0 | 9.46E-06 | 0 |
| S/N | rs768613983 |
-0.388 | None | N | 0.064 | 0.129 | 0.0401082797425 | gnomAD-4.0.0 | 4.83327E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.62442E-06 | 2.37349E-05 | 1.67235E-05 |
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 | 0.1237 | likely_benign | 0.1127 | benign | -0.768 | Destabilizing | 0.067 | N | 0.39 | neutral | None | None | None | None | N |
| S/C | 0.1447 | likely_benign | 0.1279 | benign | -0.542 | Destabilizing | 0.915 | D | 0.425 | neutral | N | 0.48176772 | None | None | N |
| S/D | 0.1673 | likely_benign | 0.1761 | benign | -0.194 | Destabilizing | 0.081 | N | 0.333 | neutral | None | None | None | None | N |
| S/E | 0.3431 | ambiguous | 0.3474 | ambiguous | -0.229 | Destabilizing | 0.081 | N | 0.326 | neutral | None | None | None | None | N |
| S/F | 0.3405 | ambiguous | 0.2996 | benign | -1.093 | Destabilizing | 0.38 | N | 0.471 | neutral | None | None | None | None | N |
| S/G | 0.0942 | likely_benign | 0.0902 | benign | -0.97 | Destabilizing | 0.027 | N | 0.375 | neutral | N | 0.48396637 | None | None | N |
| S/H | 0.214 | likely_benign | 0.206 | benign | -1.474 | Destabilizing | 0.001 | N | 0.223 | neutral | None | None | None | None | N |
| S/I | 0.3902 | ambiguous | 0.3358 | benign | -0.343 | Destabilizing | None | N | 0.31 | neutral | N | 0.487590616 | None | None | N |
| S/K | 0.4785 | ambiguous | 0.4655 | ambiguous | -0.673 | Destabilizing | 0.081 | N | 0.342 | neutral | None | None | None | None | N |
| S/L | 0.2308 | likely_benign | 0.2013 | benign | -0.343 | Destabilizing | 0.012 | N | 0.446 | neutral | None | None | None | None | N |
| S/M | 0.2511 | likely_benign | 0.216 | benign | 0.012 | Stabilizing | 0.38 | N | 0.435 | neutral | None | None | None | None | N |
| S/N | 0.0602 | likely_benign | 0.0597 | benign | -0.551 | Destabilizing | None | N | 0.064 | neutral | N | 0.40952454 | None | None | N |
| S/P | 0.8537 | likely_pathogenic | 0.8524 | pathogenic | -0.454 | Destabilizing | 0.555 | D | 0.475 | neutral | None | None | None | None | N |
| S/Q | 0.3483 | ambiguous | 0.3327 | benign | -0.795 | Destabilizing | 0.38 | N | 0.39 | neutral | None | None | None | None | N |
| S/R | 0.4675 | ambiguous | 0.4518 | ambiguous | -0.508 | Destabilizing | 0.117 | N | 0.471 | neutral | N | 0.480117989 | None | None | N |
| S/T | 0.0865 | likely_benign | 0.0801 | benign | -0.634 | Destabilizing | 0.027 | N | 0.371 | neutral | N | 0.437841718 | None | None | N |
| S/V | 0.3736 | ambiguous | 0.3232 | benign | -0.454 | Destabilizing | 0.029 | N | 0.431 | neutral | None | None | None | None | N |
| S/W | 0.4401 | ambiguous | 0.4278 | ambiguous | -1.018 | Destabilizing | 0.935 | D | 0.565 | neutral | None | None | None | None | N |
| S/Y | 0.1905 | likely_benign | 0.1713 | benign | -0.767 | Destabilizing | 0.38 | N | 0.491 | 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.