Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27686 | 83281;83282;83283 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| N2AB | 26045 | 78358;78359;78360 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| N2A | 25118 | 75577;75578;75579 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| N2B | 18621 | 56086;56087;56088 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| Novex-1 | 18746 | 56461;56462;56463 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| Novex-2 | 18813 | 56662;56663;56664 | chr2:178563076;178563075;178563074 | chr2:179427803;179427802;179427801 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs56309296  |
0.062 | None | N | 0.161 | 0.155 | None | gnomAD-2.1.1 | 5.99809E-03 | None | None | None | None | I | None | 6.42107E-02 | 2.45971E-03 | None | 0 | 0 | None | 2.28758E-04 | None | 0 | 1.79522E-04 | 1.54278E-03 |
| V/I | rs56309296 |
0.062 | None | N | 0.161 | 0.155 | None | gnomAD-3.1.2 | 1.80159E-02 | None | None | None | None | I | None | 6.32306E-02 | 5.05051E-03 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 2.49919E-04 | 6.21375E-04 | 1.14613E-02 |
| V/I | rs56309296 |
0.062 | None | N | 0.161 | 0.155 | None | 1000 genomes | 1.61741E-02 | None | None | None | None | I | None | 5.67E-02 | 8.6E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs56309296 |
0.062 | None | N | 0.161 | 0.155 | None | gnomAD-4.0.0 | 3.41703E-03 | None | None | None | None | I | None | 6.51455E-02 | 3.41735E-03 | None | 0 | 0 | None | 0 | 1.81578E-03 | 8.56137E-05 | 2.30567E-04 | 4.65779E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2269 | likely_benign | 0.2469 | benign | -0.849 | Destabilizing | 0.005 | N | 0.169 | neutral | N | 0.512876273 | None | None | I |
| V/C | 0.6542 | likely_pathogenic | 0.6657 | pathogenic | -0.824 | Destabilizing | 0.356 | N | 0.316 | neutral | None | None | None | None | I |
| V/D | 0.6431 | likely_pathogenic | 0.6326 | pathogenic | -0.559 | Destabilizing | 0.029 | N | 0.371 | neutral | N | 0.485278391 | None | None | I |
| V/E | 0.5184 | ambiguous | 0.5181 | ambiguous | -0.585 | Destabilizing | 0.072 | N | 0.343 | neutral | None | None | None | None | I |
| V/F | 0.2369 | likely_benign | 0.2212 | benign | -0.609 | Destabilizing | 0.13 | N | 0.418 | neutral | N | 0.486292349 | None | None | I |
| V/G | 0.3426 | ambiguous | 0.3556 | ambiguous | -1.097 | Destabilizing | 0.024 | N | 0.329 | neutral | N | 0.50849798 | None | None | I |
| V/H | 0.6527 | likely_pathogenic | 0.6303 | pathogenic | -0.478 | Destabilizing | 0.356 | N | 0.325 | neutral | None | None | None | None | I |
| V/I | 0.0716 | likely_benign | 0.0741 | benign | -0.3 | Destabilizing | None | N | 0.161 | neutral | N | 0.446384709 | None | None | I |
| V/K | 0.655 | likely_pathogenic | 0.6276 | pathogenic | -0.867 | Destabilizing | 0.072 | N | 0.343 | neutral | None | None | None | None | I |
| V/L | 0.1877 | likely_benign | 0.1856 | benign | -0.3 | Destabilizing | None | N | 0.195 | neutral | N | 0.520015676 | None | None | I |
| V/M | 0.1425 | likely_benign | 0.1565 | benign | -0.445 | Destabilizing | 0.214 | N | 0.273 | neutral | None | None | None | None | I |
| V/N | 0.2354 | likely_benign | 0.243 | benign | -0.754 | Destabilizing | None | N | 0.196 | neutral | None | None | None | None | I |
| V/P | 0.7499 | likely_pathogenic | 0.7606 | pathogenic | -0.447 | Destabilizing | 0.136 | N | 0.409 | neutral | None | None | None | None | I |
| V/Q | 0.4323 | ambiguous | 0.433 | ambiguous | -0.889 | Destabilizing | 0.356 | N | 0.41 | neutral | None | None | None | None | I |
| V/R | 0.6371 | likely_pathogenic | 0.5775 | pathogenic | -0.362 | Destabilizing | 0.072 | N | 0.431 | neutral | None | None | None | None | I |
| V/S | 0.1899 | likely_benign | 0.2029 | benign | -1.208 | Destabilizing | 0.001 | N | 0.203 | neutral | None | None | None | None | I |
| V/T | 0.12 | likely_benign | 0.136 | benign | -1.122 | Destabilizing | None | N | 0.155 | neutral | None | None | None | None | I |
| V/W | 0.8979 | likely_pathogenic | 0.8849 | pathogenic | -0.761 | Destabilizing | 0.864 | D | 0.322 | neutral | None | None | None | None | I |
| V/Y | 0.6109 | likely_pathogenic | 0.5761 | pathogenic | -0.467 | Destabilizing | 0.356 | N | 0.373 | neutral | None | None | 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.