Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14154 | 42685;42686;42687 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| N2AB | 12513 | 37762;37763;37764 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| N2A | 11586 | 34981;34982;34983 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| N2B | 5089 | 15490;15491;15492 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| Novex-1 | 5214 | 15865;15866;15867 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| Novex-2 | 5281 | 16066;16067;16068 | chr2:178634039;178634038;178634037 | chr2:179498766;179498765;179498764 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs752701347  |
0.118 | 0.996 | N | 0.631 | 0.287 | 0.461759001683 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/E | rs752701347 |
0.118 | 0.996 | N | 0.631 | 0.287 | 0.461759001683 | gnomAD-4.0.0 | 1.59257E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7115 | likely_pathogenic | 0.536 | ambiguous | -0.056 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| K/C | 0.9136 | likely_pathogenic | 0.8586 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| K/D | 0.9243 | likely_pathogenic | 0.8552 | pathogenic | 0.008 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| K/E | 0.4269 | ambiguous | 0.2847 | benign | 0.046 | Stabilizing | 0.996 | D | 0.631 | neutral | N | 0.509962453 | None | None | N |
| K/F | 0.9171 | likely_pathogenic | 0.8658 | pathogenic | -0.108 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| K/G | 0.8268 | likely_pathogenic | 0.7112 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| K/H | 0.627 | likely_pathogenic | 0.5291 | ambiguous | -0.453 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| K/I | 0.6511 | likely_pathogenic | 0.4662 | ambiguous | 0.5 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.514592074 | None | None | N |
| K/L | 0.5663 | likely_pathogenic | 0.437 | ambiguous | 0.5 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| K/M | 0.4473 | ambiguous | 0.3014 | benign | 0.095 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| K/N | 0.7927 | likely_pathogenic | 0.6297 | pathogenic | -0.105 | Destabilizing | 0.999 | D | 0.665 | neutral | N | 0.513210539 | None | None | N |
| K/P | 0.8773 | likely_pathogenic | 0.799 | pathogenic | 0.344 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | N |
| K/Q | 0.2997 | likely_benign | 0.214 | benign | -0.2 | Destabilizing | 0.999 | D | 0.659 | neutral | N | 0.49896564 | None | None | N |
| K/R | 0.1124 | likely_benign | 0.0996 | benign | -0.202 | Destabilizing | 0.64 | D | 0.299 | neutral | N | 0.507856002 | None | None | N |
| K/S | 0.8122 | likely_pathogenic | 0.659 | pathogenic | -0.58 | Destabilizing | 0.998 | D | 0.658 | neutral | None | None | None | None | N |
| K/T | 0.4579 | ambiguous | 0.2824 | benign | -0.38 | Destabilizing | 0.999 | D | 0.635 | neutral | N | 0.508228296 | None | None | N |
| K/V | 0.6358 | likely_pathogenic | 0.4566 | ambiguous | 0.344 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/W | 0.9173 | likely_pathogenic | 0.8907 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| K/Y | 0.8656 | likely_pathogenic | 0.8 | pathogenic | 0.205 | Stabilizing | 1.0 | D | 0.696 | prob.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.