Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26082 | 78469;78470;78471 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| N2AB | 24441 | 73546;73547;73548 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| N2A | 23514 | 70765;70766;70767 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| N2B | 17017 | 51274;51275;51276 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| Novex-1 | 17142 | 51649;51650;51651 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| Novex-2 | 17209 | 51850;51851;51852 | chr2:178567888;178567887;178567886 | chr2:179432615;179432614;179432613 |
| 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/G | rs794727452  |
None | 0.001 | N | 0.355 | 0.256 | 0.60213386617 | gnomAD-4.0.0 | 2.05288E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69874E-06 | 0 | 0 |
| C/S | rs794727452 |
-1.648 | 0.495 | N | 0.436 | 0.23 | 0.476445137733 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| C/S | rs794727452 |
-1.648 | 0.495 | N | 0.436 | 0.23 | 0.476445137733 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| C/S | rs794727452 |
-1.648 | 0.495 | N | 0.436 | 0.23 | 0.476445137733 | gnomAD-4.0.0 | 1.23959E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69548E-05 | 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 | 0.2422 | likely_benign | 0.2082 | benign | -1.633 | Destabilizing | 0.221 | N | 0.272 | neutral | None | None | None | None | N |
| C/D | 0.6646 | likely_pathogenic | 0.6322 | pathogenic | -0.087 | Destabilizing | 0.864 | D | 0.673 | prob.neutral | None | None | None | None | N |
| C/E | 0.7527 | likely_pathogenic | 0.7339 | pathogenic | -0.014 | Destabilizing | 0.951 | D | 0.663 | prob.neutral | None | None | None | None | N |
| C/F | 0.1676 | likely_benign | 0.1583 | benign | -1.01 | Destabilizing | 0.704 | D | 0.621 | neutral | N | 0.44818921 | None | None | N |
| C/G | 0.1056 | likely_benign | 0.083 | benign | -1.916 | Destabilizing | 0.001 | N | 0.355 | neutral | N | 0.433993336 | None | None | N |
| C/H | 0.4576 | ambiguous | 0.4452 | ambiguous | -1.794 | Destabilizing | 0.996 | D | 0.571 | neutral | None | None | None | None | N |
| C/I | 0.3094 | likely_benign | 0.3004 | benign | -0.918 | Destabilizing | 0.017 | N | 0.345 | neutral | None | None | None | None | N |
| C/K | 0.725 | likely_pathogenic | 0.7112 | pathogenic | -0.849 | Destabilizing | 0.864 | D | 0.663 | prob.neutral | None | None | None | None | N |
| C/L | 0.3047 | likely_benign | 0.3329 | benign | -0.918 | Destabilizing | 0.004 | N | 0.283 | neutral | None | None | None | None | N |
| C/M | 0.4814 | ambiguous | 0.4612 | ambiguous | -0.1 | Destabilizing | 0.917 | D | 0.484 | neutral | None | None | None | None | N |
| C/N | 0.3289 | likely_benign | 0.2962 | benign | -0.703 | Destabilizing | 0.864 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/P | 0.3163 | likely_benign | 0.2849 | benign | -1.13 | Destabilizing | 0.986 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/Q | 0.5607 | ambiguous | 0.5409 | ambiguous | -0.687 | Destabilizing | 0.986 | D | 0.605 | neutral | None | None | None | None | N |
| C/R | 0.4351 | ambiguous | 0.4314 | ambiguous | -0.596 | Destabilizing | 0.981 | D | 0.681 | prob.neutral | N | 0.469991422 | None | None | N |
| C/S | 0.1862 | likely_benign | 0.1506 | benign | -1.306 | Destabilizing | 0.495 | N | 0.436 | neutral | N | 0.369808571 | None | None | N |
| C/T | 0.3264 | likely_benign | 0.2855 | benign | -1.059 | Destabilizing | 0.565 | D | 0.434 | neutral | None | None | None | None | N |
| C/V | 0.2731 | likely_benign | 0.2682 | benign | -1.13 | Destabilizing | 0.017 | N | 0.292 | neutral | None | None | None | None | N |
| C/W | 0.4284 | ambiguous | 0.4327 | ambiguous | -0.937 | Destabilizing | 0.995 | D | 0.551 | neutral | N | 0.50750966 | None | None | N |
| C/Y | 0.2163 | likely_benign | 0.2105 | benign | -0.947 | Destabilizing | 0.981 | D | 0.609 | neutral | N | 0.469471347 | 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.