Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3241 | 9946;9947;9948 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| N2AB | 3241 | 9946;9947;9948 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| N2A | 3241 | 9946;9947;9948 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| N2B | 3195 | 9808;9809;9810 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| Novex-1 | 3195 | 9808;9809;9810 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| Novex-2 | 3195 | 9808;9809;9810 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
| Novex-3 | 3241 | 9946;9947;9948 | chr2:178764794;178764793;178764792 | chr2:179629521;179629520;179629519 |
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/L | rs777535305  |
-0.611 | None | N | 0.258 | 0.14 | 0.143124449307 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 6.19E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs777535305 |
-0.611 | None | N | 0.258 | 0.14 | 0.143124449307 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs777535305 |
-0.611 | None | N | 0.258 | 0.14 | 0.143124449307 | gnomAD-4.0.0 | 3.84561E-06 | None | None | None | None | N | None | 5.07563E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.498 | ambiguous | 0.703 | pathogenic | -1.425 | Destabilizing | 0.052 | N | 0.547 | neutral | N | 0.513050272 | None | None | N |
| V/C | 0.7729 | likely_pathogenic | 0.8916 | pathogenic | -0.952 | Destabilizing | 0.935 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/D | 0.8327 | likely_pathogenic | 0.9496 | pathogenic | -1.203 | Destabilizing | 0.484 | N | 0.812 | deleterious | N | 0.516873215 | None | None | N |
| V/E | 0.766 | likely_pathogenic | 0.9058 | pathogenic | -1.219 | Destabilizing | 0.555 | D | 0.767 | deleterious | None | None | None | None | N |
| V/F | 0.1645 | likely_benign | 0.2981 | benign | -1.114 | Destabilizing | 0.317 | N | 0.69 | prob.neutral | N | 0.318297772 | None | None | N |
| V/G | 0.5998 | likely_pathogenic | 0.8118 | pathogenic | -1.722 | Destabilizing | 0.484 | N | 0.788 | deleterious | N | 0.516465873 | None | None | N |
| V/H | 0.8241 | likely_pathogenic | 0.9454 | pathogenic | -1.248 | Destabilizing | 0.935 | D | 0.819 | deleterious | None | None | None | None | N |
| V/I | 0.0507 | likely_benign | 0.0526 | benign | -0.716 | Destabilizing | None | N | 0.195 | neutral | N | 0.320810072 | None | None | N |
| V/K | 0.7719 | likely_pathogenic | 0.9187 | pathogenic | -1.154 | Destabilizing | 0.555 | D | 0.768 | deleterious | None | None | None | None | N |
| V/L | 0.1445 | likely_benign | 0.2193 | benign | -0.716 | Destabilizing | None | N | 0.258 | neutral | N | 0.43243395 | None | None | N |
| V/M | 0.1684 | likely_benign | 0.2627 | benign | -0.582 | Destabilizing | 0.38 | N | 0.58 | neutral | None | None | None | None | N |
| V/N | 0.6091 | likely_pathogenic | 0.8494 | pathogenic | -0.909 | Destabilizing | 0.791 | D | 0.822 | deleterious | None | None | None | None | N |
| V/P | 0.6259 | likely_pathogenic | 0.8054 | pathogenic | -0.918 | Destabilizing | 0.791 | D | 0.8 | deleterious | None | None | None | None | N |
| V/Q | 0.7675 | likely_pathogenic | 0.9075 | pathogenic | -1.109 | Destabilizing | 0.791 | D | 0.804 | deleterious | None | None | None | None | N |
| V/R | 0.7136 | likely_pathogenic | 0.8959 | pathogenic | -0.637 | Destabilizing | 0.555 | D | 0.823 | deleterious | None | None | None | None | N |
| V/S | 0.5862 | likely_pathogenic | 0.8206 | pathogenic | -1.418 | Destabilizing | 0.262 | N | 0.763 | deleterious | None | None | None | None | N |
| V/T | 0.5598 | ambiguous | 0.7617 | pathogenic | -1.333 | Destabilizing | 0.149 | N | 0.553 | neutral | None | None | None | None | N |
| V/W | 0.8434 | likely_pathogenic | 0.94 | pathogenic | -1.267 | Destabilizing | 0.935 | D | 0.822 | deleterious | None | None | None | None | N |
| V/Y | 0.6166 | likely_pathogenic | 0.8173 | pathogenic | -0.988 | Destabilizing | 0.555 | D | 0.697 | prob.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.