Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15613 | 47062;47063;47064 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| N2AB | 13972 | 42139;42140;42141 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| N2A | 13045 | 39358;39359;39360 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| N2B | 6548 | 19867;19868;19869 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| Novex-1 | 6673 | 20242;20243;20244 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| Novex-2 | 6740 | 20443;20444;20445 | chr2:178618713;178618712;178618711 | chr2:179483440;179483439;179483438 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs879064998  |
-0.809 | 0.062 | N | 0.406 | 0.217 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.58762E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs879064998 |
-0.809 | 0.062 | N | 0.406 | 0.217 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 1.94704E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs879064998 |
-0.809 | 0.062 | N | 0.406 | 0.217 | None | gnomAD-4.0.0 | 1.31705E-05 | None | None | None | None | N | None | 2.41651E-05 | 0 | None | 0 | 1.94704E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1428 | likely_benign | 0.2486 | benign | -2.219 | Highly Destabilizing | 0.035 | N | 0.349 | neutral | None | None | None | None | N |
| I/C | 0.5495 | ambiguous | 0.6757 | pathogenic | -1.879 | Destabilizing | 0.824 | D | 0.428 | neutral | None | None | None | None | N |
| I/D | 0.605 | likely_pathogenic | 0.8167 | pathogenic | -2.22 | Highly Destabilizing | 0.555 | D | 0.557 | neutral | None | None | None | None | N |
| I/E | 0.3895 | ambiguous | 0.577 | pathogenic | -2.061 | Highly Destabilizing | 0.555 | D | 0.552 | neutral | None | None | None | None | N |
| I/F | 0.1794 | likely_benign | 0.2464 | benign | -1.485 | Destabilizing | 0.317 | N | 0.387 | neutral | N | 0.490265779 | None | None | N |
| I/G | 0.4015 | ambiguous | 0.6271 | pathogenic | -2.702 | Highly Destabilizing | 0.262 | N | 0.543 | neutral | None | None | None | None | N |
| I/H | 0.4749 | ambiguous | 0.6238 | pathogenic | -2.16 | Highly Destabilizing | 0.935 | D | 0.526 | neutral | None | None | None | None | N |
| I/K | 0.2342 | likely_benign | 0.343 | ambiguous | -1.464 | Destabilizing | 0.555 | D | 0.555 | neutral | None | None | None | None | N |
| I/L | 0.1234 | likely_benign | 0.1647 | benign | -0.861 | Destabilizing | 0.005 | N | 0.253 | neutral | N | 0.490136297 | None | None | N |
| I/M | 0.0898 | likely_benign | 0.1149 | benign | -0.969 | Destabilizing | 0.317 | N | 0.437 | neutral | N | 0.49357741 | None | None | N |
| I/N | 0.2592 | likely_benign | 0.4118 | ambiguous | -1.644 | Destabilizing | 0.741 | D | 0.551 | neutral | N | 0.494567199 | None | None | N |
| I/P | 0.6482 | likely_pathogenic | 0.8016 | pathogenic | -1.291 | Destabilizing | 0.555 | D | 0.551 | neutral | None | None | None | None | N |
| I/Q | 0.2971 | likely_benign | 0.432 | ambiguous | -1.614 | Destabilizing | 0.791 | D | 0.555 | neutral | None | None | None | None | N |
| I/R | 0.1956 | likely_benign | 0.2697 | benign | -1.186 | Destabilizing | 0.555 | D | 0.555 | neutral | None | None | None | None | N |
| I/S | 0.2027 | likely_benign | 0.3301 | benign | -2.391 | Highly Destabilizing | 0.117 | N | 0.487 | neutral | N | 0.493701351 | None | None | N |
| I/T | 0.089 | likely_benign | 0.1517 | benign | -2.088 | Highly Destabilizing | 0.062 | N | 0.406 | neutral | N | 0.475355537 | None | None | N |
| I/V | 0.0572 | likely_benign | 0.0707 | benign | -1.291 | Destabilizing | None | N | 0.12 | neutral | N | 0.384005192 | None | None | N |
| I/W | 0.7113 | likely_pathogenic | 0.804 | pathogenic | -1.761 | Destabilizing | 0.935 | D | 0.585 | neutral | None | None | None | None | N |
| I/Y | 0.4748 | ambiguous | 0.5677 | pathogenic | -1.462 | Destabilizing | 0.555 | D | 0.463 | 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.