Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8955 | 27088;27089;27090 | chr2:178713271;178713270;178713269 | chr2:179577998;179577997;179577996 |
| N2AB | 8638 | 26137;26138;26139 | chr2:178713271;178713270;178713269 | chr2:179577998;179577997;179577996 |
| N2A | 7711 | 23356;23357;23358 | chr2:178713271;178713270;178713269 | chr2:179577998;179577997;179577996 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/V | rs72648994  |
-1.498 | 0.677 | N | 0.359 | 0.094 | None | gnomAD-2.1.1 | 3.78195E-03 | None | None | None | None | N | None | 8.39E-05 | 1.44159E-04 | None | 0 | 0 | None | 7.2337E-03 | None | 2.60887E-02 | 1.1886E-03 | 3E-03 |
| I/V | rs72648994 |
-1.498 | 0.677 | N | 0.359 | 0.094 | None | gnomAD-3.1.2 | 2.72132E-03 | None | None | None | None | N | None | 9.65E-05 | 1.96515E-04 | 0 | 0 | 0 | None | 2.69608E-02 | 0 | 1.35278E-03 | 5.80431E-03 | 4.78011E-04 |
| I/V | rs72648994 |
-1.498 | 0.677 | N | 0.359 | 0.094 | None | 1000 genomes | 2.19649E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 4E-03 | None | None | None | 7.2E-03 | None |
| I/V | rs72648994 |
-1.498 | 0.677 | N | 0.359 | 0.094 | None | gnomAD-4.0.0 | 2.25398E-03 | None | None | None | None | N | None | 1.46631E-04 | 1.34197E-04 | None | 0 | 0 | None | 2.67376E-02 | 2.47688E-03 | 9.86148E-04 | 7.09973E-03 | 1.3624E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8512 | likely_pathogenic | 0.8923 | pathogenic | -1.916 | Destabilizing | 0.927 | D | 0.543 | neutral | None | None | None | None | N |
| I/C | 0.9554 | likely_pathogenic | 0.9703 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| I/D | 0.9928 | likely_pathogenic | 0.9959 | pathogenic | -1.384 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | None | None | None | None | N |
| I/E | 0.9871 | likely_pathogenic | 0.9921 | pathogenic | -1.367 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/F | 0.3937 | ambiguous | 0.4633 | ambiguous | -1.42 | Destabilizing | 0.068 | N | 0.34 | neutral | N | 0.476531471 | None | None | N |
| I/G | 0.9788 | likely_pathogenic | 0.9869 | pathogenic | -2.261 | Highly Destabilizing | 0.995 | D | 0.72 | prob.delet. | None | None | None | None | N |
| I/H | 0.9695 | likely_pathogenic | 0.9821 | pathogenic | -1.52 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/K | 0.9636 | likely_pathogenic | 0.9773 | pathogenic | -1.325 | Destabilizing | 0.995 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/L | 0.1805 | likely_benign | 0.2041 | benign | -1.027 | Destabilizing | 0.01 | N | 0.104 | neutral | N | 0.407860819 | None | None | N |
| I/M | 0.2308 | likely_benign | 0.2683 | benign | -0.81 | Destabilizing | 0.677 | D | 0.353 | neutral | N | 0.409461117 | None | None | N |
| I/N | 0.9247 | likely_pathogenic | 0.956 | pathogenic | -1.156 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | N | 0.49977369 | None | None | N |
| I/P | 0.9315 | likely_pathogenic | 0.9453 | pathogenic | -1.293 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9663 | likely_pathogenic | 0.9775 | pathogenic | -1.331 | Destabilizing | 0.995 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/R | 0.94 | likely_pathogenic | 0.9616 | pathogenic | -0.751 | Destabilizing | 0.995 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/S | 0.908 | likely_pathogenic | 0.9407 | pathogenic | -1.808 | Destabilizing | 0.979 | D | 0.662 | neutral | N | 0.461986093 | None | None | N |
| I/T | 0.9045 | likely_pathogenic | 0.9402 | pathogenic | -1.671 | Destabilizing | 0.979 | D | 0.593 | neutral | N | 0.461986093 | None | None | N |
| I/V | 0.1015 | likely_benign | 0.1152 | benign | -1.293 | Destabilizing | 0.677 | D | 0.359 | neutral | N | 0.447555358 | None | None | N |
| I/W | 0.9721 | likely_pathogenic | 0.9818 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| I/Y | 0.8841 | likely_pathogenic | 0.9199 | pathogenic | -1.273 | Destabilizing | 0.982 | D | 0.664 | 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.