Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21800 | 65623;65624;65625 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| N2AB | 20159 | 60700;60701;60702 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| N2A | 19232 | 57919;57920;57921 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| N2B | 12735 | 38428;38429;38430 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| Novex-1 | 12860 | 38803;38804;38805 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| Novex-2 | 12927 | 39004;39005;39006 | chr2:178583784;178583783;178583782 | chr2:179448511;179448510;179448509 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs760650311  |
None | 0.322 | N | 0.36 | 0.223 | 0.143124449307 | gnomAD-4.0.0 | 2.74218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60198E-06 | 0 | 0 |
| P/T | rs760650311 |
-0.363 | 0.885 | N | 0.454 | 0.268 | 0.307332253619 | gnomAD-2.1.1 | 8.21E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.82E-05 | 0 |
| P/T | rs760650311 |
-0.363 | 0.885 | N | 0.454 | 0.268 | 0.307332253619 | gnomAD-4.0.0 | 2.74218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60198E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1613 | likely_benign | 0.1337 | benign | -0.471 | Destabilizing | 0.885 | D | 0.471 | neutral | N | 0.469532849 | None | None | N |
| P/C | 0.6582 | likely_pathogenic | 0.5793 | pathogenic | -0.948 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| P/D | 0.4306 | ambiguous | 0.3942 | ambiguous | -0.409 | Destabilizing | 0.986 | D | 0.427 | neutral | None | None | None | None | N |
| P/E | 0.3507 | ambiguous | 0.3214 | benign | -0.513 | Destabilizing | 0.953 | D | 0.458 | neutral | None | None | None | None | N |
| P/F | 0.765 | likely_pathogenic | 0.6901 | pathogenic | -0.797 | Destabilizing | 0.998 | D | 0.583 | neutral | None | None | None | None | N |
| P/G | 0.2886 | likely_benign | 0.2474 | benign | -0.522 | Destabilizing | 0.91 | D | 0.447 | neutral | None | None | None | None | N |
| P/H | 0.3418 | ambiguous | 0.2859 | benign | -0.041 | Destabilizing | 0.999 | D | 0.531 | neutral | N | 0.507051087 | None | None | N |
| P/I | 0.6159 | likely_pathogenic | 0.54 | ambiguous | -0.464 | Destabilizing | 0.993 | D | 0.609 | neutral | None | None | None | None | N |
| P/K | 0.4583 | ambiguous | 0.4124 | ambiguous | -0.509 | Destabilizing | 0.386 | N | 0.359 | neutral | None | None | None | None | N |
| P/L | 0.3018 | likely_benign | 0.2457 | benign | -0.464 | Destabilizing | 0.982 | D | 0.55 | neutral | N | 0.511822188 | None | None | N |
| P/M | 0.5714 | likely_pathogenic | 0.4869 | ambiguous | -0.757 | Destabilizing | 0.999 | D | 0.537 | neutral | None | None | None | None | N |
| P/N | 0.4218 | ambiguous | 0.3551 | ambiguous | -0.364 | Destabilizing | 0.986 | D | 0.539 | neutral | None | None | None | None | N |
| P/Q | 0.288 | likely_benign | 0.2423 | benign | -0.548 | Destabilizing | 0.986 | D | 0.48 | neutral | None | None | None | None | N |
| P/R | 0.3129 | likely_benign | 0.2729 | benign | -0.068 | Destabilizing | 0.964 | D | 0.539 | neutral | N | 0.501797196 | None | None | N |
| P/S | 0.2255 | likely_benign | 0.1872 | benign | -0.682 | Destabilizing | 0.322 | N | 0.36 | neutral | N | 0.462124087 | None | None | N |
| P/T | 0.1977 | likely_benign | 0.1611 | benign | -0.697 | Destabilizing | 0.885 | D | 0.454 | neutral | N | 0.481325923 | None | None | N |
| P/V | 0.4487 | ambiguous | 0.3847 | ambiguous | -0.441 | Destabilizing | 0.986 | D | 0.491 | neutral | None | None | None | None | N |
| P/W | 0.7945 | likely_pathogenic | 0.7473 | pathogenic | -0.829 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/Y | 0.655 | likely_pathogenic | 0.5744 | pathogenic | -0.593 | Destabilizing | 0.999 | D | 0.586 | 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.