Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24444 | 73555;73556;73557 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| N2AB | 22803 | 68632;68633;68634 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| N2A | 21876 | 65851;65852;65853 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| N2B | 15379 | 46360;46361;46362 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| Novex-1 | 15504 | 46735;46736;46737 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| Novex-2 | 15571 | 46936;46937;46938 | chr2:178572802;178572801;178572800 | chr2:179437529;179437528;179437527 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 0.521 | N | 0.553 | 0.288 | 0.541557034822 | gnomAD-4.0.0 | 1.59193E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85953E-06 | 0 | 0 |
| C/S | rs760672834  |
-0.801 | 0.034 | N | 0.147 | 0.245 | 0.278143212241 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2543 | likely_benign | 0.2666 | benign | -1.122 | Destabilizing | 0.206 | N | 0.276 | neutral | None | None | None | None | I |
| C/D | 0.5815 | likely_pathogenic | 0.6236 | pathogenic | 0.126 | Stabilizing | 0.742 | D | 0.531 | neutral | None | None | None | None | I |
| C/E | 0.7637 | likely_pathogenic | 0.7848 | pathogenic | 0.133 | Stabilizing | 0.59 | D | 0.507 | neutral | None | None | None | None | I |
| C/F | 0.3038 | likely_benign | 0.3381 | benign | -0.907 | Destabilizing | 0.979 | D | 0.503 | neutral | N | 0.446087481 | None | None | I |
| C/G | 0.1008 | likely_benign | 0.1018 | benign | -1.329 | Destabilizing | 0.472 | N | 0.496 | neutral | N | 0.303671219 | None | None | I |
| C/H | 0.4766 | ambiguous | 0.4861 | ambiguous | -1.423 | Destabilizing | 0.953 | D | 0.496 | neutral | None | None | None | None | I |
| C/I | 0.6307 | likely_pathogenic | 0.6854 | pathogenic | -0.642 | Destabilizing | 0.854 | D | 0.454 | neutral | None | None | None | None | I |
| C/K | 0.805 | likely_pathogenic | 0.8202 | pathogenic | -0.311 | Destabilizing | 0.59 | D | 0.504 | neutral | None | None | None | None | I |
| C/L | 0.46 | ambiguous | 0.4959 | ambiguous | -0.642 | Destabilizing | 0.543 | D | 0.415 | neutral | None | None | None | None | I |
| C/M | 0.5527 | ambiguous | 0.5871 | pathogenic | -0.092 | Destabilizing | 0.953 | D | 0.411 | neutral | None | None | None | None | I |
| C/N | 0.2822 | likely_benign | 0.2819 | benign | -0.041 | Destabilizing | 0.742 | D | 0.547 | neutral | None | None | None | None | I |
| C/P | 0.9682 | likely_pathogenic | 0.9718 | pathogenic | -0.777 | Destabilizing | 0.953 | D | 0.547 | neutral | None | None | None | None | I |
| C/Q | 0.5546 | ambiguous | 0.5592 | ambiguous | -0.169 | Destabilizing | 0.037 | N | 0.313 | neutral | None | None | None | None | I |
| C/R | 0.5272 | ambiguous | 0.552 | ambiguous | -0.051 | Destabilizing | 0.521 | D | 0.553 | neutral | N | 0.392522355 | None | None | I |
| C/S | 0.1397 | likely_benign | 0.1393 | benign | -0.546 | Destabilizing | 0.034 | N | 0.147 | neutral | N | 0.316984446 | None | None | I |
| C/T | 0.3024 | likely_benign | 0.3108 | benign | -0.391 | Destabilizing | 0.373 | N | 0.415 | neutral | None | None | None | None | I |
| C/V | 0.4706 | ambiguous | 0.5175 | ambiguous | -0.777 | Destabilizing | 0.742 | D | 0.453 | neutral | None | None | None | None | I |
| C/W | 0.6832 | likely_pathogenic | 0.7266 | pathogenic | -0.839 | Destabilizing | 0.994 | D | 0.499 | neutral | N | 0.446087481 | None | None | I |
| C/Y | 0.3686 | ambiguous | 0.4053 | ambiguous | -0.759 | Destabilizing | 0.979 | D | 0.504 | neutral | N | 0.445914122 | None | None | I |
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.