Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33388 | 100387;100388;100389 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| N2AB | 31747 | 95464;95465;95466 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| N2A | 30820 | 92683;92684;92685 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| N2B | 24323 | 73192;73193;73194 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| Novex-1 | 24448 | 73567;73568;73569 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| Novex-2 | 24515 | 73768;73769;73770 | chr2:178536947;178536946;178536945 | chr2:179401674;179401673;179401672 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.181 | N | 0.463 | 0.08 | 0.126345400529 | gnomAD-4.0.0 | 1.61255E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.90781E-06 | 0 | 0 |
| S/N | rs745406517  |
0.018 | 0.181 | N | 0.507 | 0.074 | None | gnomAD-2.1.1 | 1.09E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.38E-05 | 0 |
| S/N | rs745406517 |
0.018 | 0.181 | N | 0.507 | 0.074 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| S/N | rs745406517 |
0.018 | 0.181 | N | 0.507 | 0.074 | None | gnomAD-4.0.0 | 1.12185E-05 | None | None | None | None | I | None | 1.33765E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44892E-05 | 0 | 0 |
| S/R | None | None | 0.437 | N | 0.518 | 0.177 | 0.262175524916 | gnomAD-4.0.0 | 2.40094E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62532E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1533 | likely_benign | 0.1628 | benign | -0.053 | Destabilizing | 0.057 | N | 0.482 | neutral | None | None | None | None | I |
| S/C | 0.2343 | likely_benign | 0.2525 | benign | -0.427 | Destabilizing | 0.856 | D | 0.454 | neutral | N | 0.46533775 | None | None | I |
| S/D | 0.5898 | likely_pathogenic | 0.6974 | pathogenic | 0.149 | Stabilizing | 0.227 | N | 0.458 | neutral | None | None | None | None | I |
| S/E | 0.729 | likely_pathogenic | 0.8124 | pathogenic | 0.064 | Stabilizing | 0.227 | N | 0.451 | neutral | None | None | None | None | I |
| S/F | 0.4759 | ambiguous | 0.5305 | ambiguous | -0.654 | Destabilizing | 0.507 | D | 0.531 | neutral | None | None | None | None | I |
| S/G | 0.2236 | likely_benign | 0.2424 | benign | -0.15 | Destabilizing | 0.181 | N | 0.463 | neutral | N | 0.498255458 | None | None | I |
| S/H | 0.5369 | ambiguous | 0.6394 | pathogenic | -0.482 | Destabilizing | 0.96 | D | 0.416 | neutral | None | None | None | None | I |
| S/I | 0.4163 | ambiguous | 0.4738 | ambiguous | 0.067 | Stabilizing | 0.28 | N | 0.531 | neutral | N | 0.463046991 | None | None | I |
| S/K | 0.8852 | likely_pathogenic | 0.9351 | pathogenic | -0.401 | Destabilizing | 0.227 | N | 0.45 | neutral | None | None | None | None | I |
| S/L | 0.2222 | likely_benign | 0.2444 | benign | 0.067 | Stabilizing | 0.128 | N | 0.495 | neutral | None | None | None | None | I |
| S/M | 0.3779 | ambiguous | 0.4098 | ambiguous | -0.083 | Destabilizing | 0.057 | N | 0.423 | neutral | None | None | None | None | I |
| S/N | 0.217 | likely_benign | 0.2714 | benign | -0.223 | Destabilizing | 0.181 | N | 0.507 | neutral | N | 0.440210019 | None | None | I |
| S/P | 0.2189 | likely_benign | 0.2811 | benign | 0.056 | Stabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | I |
| S/Q | 0.6976 | likely_pathogenic | 0.7773 | pathogenic | -0.41 | Destabilizing | 0.676 | D | 0.409 | neutral | None | None | None | None | I |
| S/R | 0.8802 | likely_pathogenic | 0.932 | pathogenic | -0.162 | Destabilizing | 0.437 | N | 0.518 | neutral | N | 0.505394861 | None | None | I |
| S/T | 0.1718 | likely_benign | 0.1825 | benign | -0.289 | Destabilizing | None | N | 0.125 | neutral | N | 0.43591892 | None | None | I |
| S/V | 0.3919 | ambiguous | 0.4476 | ambiguous | 0.056 | Stabilizing | 0.128 | N | 0.45 | neutral | None | None | None | None | I |
| S/W | 0.6092 | likely_pathogenic | 0.6824 | pathogenic | -0.746 | Destabilizing | 0.96 | D | 0.682 | prob.neutral | None | None | None | None | I |
| S/Y | 0.3141 | likely_benign | 0.3926 | ambiguous | -0.419 | Destabilizing | 0.676 | D | 0.499 | 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.