Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22016 | 66271;66272;66273 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| N2AB | 20375 | 61348;61349;61350 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| N2A | 19448 | 58567;58568;58569 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| N2B | 12951 | 39076;39077;39078 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| Novex-1 | 13076 | 39451;39452;39453 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| Novex-2 | 13143 | 39652;39653;39654 | chr2:178582410;178582409;178582408 | chr2:179447137;179447136;179447135 |
| 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/I | rs1424506370  |
0.311 | 0.062 | N | 0.524 | 0.113 | 0.1749357433 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/I | rs1424506370 |
0.311 | 0.062 | N | 0.524 | 0.113 | 0.1749357433 | gnomAD-4.0.0 | 1.59316E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43365E-05 | 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 | 0.0762 | likely_benign | 0.0775 | benign | -0.333 | Destabilizing | 0.035 | N | 0.313 | neutral | None | None | None | None | N |
| S/C | 0.1186 | likely_benign | 0.1059 | benign | -0.251 | Destabilizing | 0.78 | D | 0.49 | neutral | N | 0.509150029 | None | None | N |
| S/D | 0.6295 | likely_pathogenic | 0.6388 | pathogenic | 0.088 | Stabilizing | 0.001 | N | 0.189 | neutral | None | None | None | None | N |
| S/E | 0.6444 | likely_pathogenic | 0.6874 | pathogenic | 0.029 | Stabilizing | 0.081 | N | 0.452 | neutral | None | None | None | None | N |
| S/F | 0.1923 | likely_benign | 0.2044 | benign | -0.739 | Destabilizing | 0.38 | N | 0.577 | neutral | None | None | None | None | N |
| S/G | 0.1493 | likely_benign | 0.1309 | benign | -0.508 | Destabilizing | 0.052 | N | 0.449 | neutral | N | 0.503685495 | None | None | N |
| S/H | 0.3605 | ambiguous | 0.3469 | ambiguous | -0.986 | Destabilizing | 0.935 | D | 0.504 | neutral | None | None | None | None | N |
| S/I | 0.1237 | likely_benign | 0.1311 | benign | 0.003 | Stabilizing | 0.062 | N | 0.524 | neutral | N | 0.479845843 | None | None | N |
| S/K | 0.7457 | likely_pathogenic | 0.7564 | pathogenic | -0.57 | Destabilizing | 0.149 | N | 0.407 | neutral | None | None | None | None | N |
| S/L | 0.0863 | likely_benign | 0.089 | benign | 0.003 | Stabilizing | 0.001 | N | 0.411 | neutral | None | None | None | None | N |
| S/M | 0.1401 | likely_benign | 0.1441 | benign | 0.127 | Stabilizing | 0.38 | N | 0.514 | neutral | None | None | None | None | N |
| S/N | 0.1577 | likely_benign | 0.1459 | benign | -0.31 | Destabilizing | 0.117 | N | 0.408 | neutral | N | 0.453083316 | None | None | N |
| S/P | 0.2585 | likely_benign | 0.2366 | benign | -0.077 | Destabilizing | 0.555 | D | 0.513 | neutral | None | None | None | None | N |
| S/Q | 0.5171 | ambiguous | 0.5218 | ambiguous | -0.486 | Destabilizing | 0.555 | D | 0.496 | neutral | None | None | None | None | N |
| S/R | 0.6828 | likely_pathogenic | 0.6936 | pathogenic | -0.402 | Destabilizing | 0.541 | D | 0.531 | neutral | N | 0.437807219 | None | None | N |
| S/T | 0.0622 | likely_benign | 0.069 | benign | -0.36 | Destabilizing | None | N | 0.152 | neutral | N | 0.379369417 | None | None | N |
| S/V | 0.1227 | likely_benign | 0.1316 | benign | -0.077 | Destabilizing | 0.081 | N | 0.501 | neutral | None | None | None | None | N |
| S/W | 0.3675 | ambiguous | 0.3816 | ambiguous | -0.778 | Destabilizing | 0.935 | D | 0.618 | neutral | None | None | None | None | N |
| S/Y | 0.2014 | likely_benign | 0.2092 | benign | -0.494 | Destabilizing | 0.555 | D | 0.575 | 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.