Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23932 | 72019;72020;72021 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| N2AB | 22291 | 67096;67097;67098 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| N2A | 21364 | 64315;64316;64317 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| N2B | 14867 | 44824;44825;44826 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| Novex-1 | 14992 | 45199;45200;45201 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| Novex-2 | 15059 | 45400;45401;45402 | chr2:178574338;178574337;178574336 | chr2:179439065;179439064;179439063 |
| 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 | rs1437243224  |
None | 0.001 | N | 0.141 | 0.088 | 0.0551355673512 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs1437243224 |
None | 0.001 | N | 0.141 | 0.088 | 0.0551355673512 | gnomAD-4.0.0 | 6.57557E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47059E-05 | 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 | 0.154 | likely_benign | 0.1484 | benign | -1.103 | Destabilizing | 0.165 | N | 0.445 | neutral | N | 0.486926531 | None | None | N |
| V/C | 0.6413 | likely_pathogenic | 0.6149 | pathogenic | -0.741 | Destabilizing | 0.981 | D | 0.533 | neutral | None | None | None | None | N |
| V/D | 0.27 | likely_benign | 0.2626 | benign | -0.685 | Destabilizing | 0.241 | N | 0.585 | neutral | None | None | None | None | N |
| V/E | 0.1858 | likely_benign | 0.1788 | benign | -0.673 | Destabilizing | 0.001 | N | 0.353 | neutral | N | 0.375969327 | None | None | N |
| V/F | 0.1326 | likely_benign | 0.1312 | benign | -0.727 | Destabilizing | 0.69 | D | 0.572 | neutral | None | None | None | None | N |
| V/G | 0.2334 | likely_benign | 0.2162 | benign | -1.421 | Destabilizing | 0.324 | N | 0.598 | neutral | N | 0.484849018 | None | None | N |
| V/H | 0.3969 | ambiguous | 0.3924 | ambiguous | -0.914 | Destabilizing | 0.944 | D | 0.609 | neutral | None | None | None | None | N |
| V/I | 0.0639 | likely_benign | 0.0663 | benign | -0.34 | Destabilizing | 0.001 | N | 0.141 | neutral | N | 0.487446606 | None | None | N |
| V/K | 0.242 | likely_benign | 0.2421 | benign | -0.94 | Destabilizing | 0.241 | N | 0.577 | neutral | None | None | None | None | N |
| V/L | 0.1147 | likely_benign | 0.1105 | benign | -0.34 | Destabilizing | 0.033 | N | 0.403 | neutral | N | 0.475768175 | None | None | N |
| V/M | 0.102 | likely_benign | 0.0993 | benign | -0.325 | Destabilizing | 0.69 | D | 0.497 | neutral | None | None | None | None | N |
| V/N | 0.173 | likely_benign | 0.1692 | benign | -0.782 | Destabilizing | 0.69 | D | 0.629 | neutral | None | None | None | None | N |
| V/P | 0.8114 | likely_pathogenic | 0.8191 | pathogenic | -0.558 | Destabilizing | 0.818 | D | 0.627 | neutral | None | None | None | None | N |
| V/Q | 0.2121 | likely_benign | 0.2068 | benign | -0.885 | Destabilizing | 0.527 | D | 0.621 | neutral | None | None | None | None | N |
| V/R | 0.2237 | likely_benign | 0.2262 | benign | -0.505 | Destabilizing | 0.69 | D | 0.626 | neutral | None | None | None | None | N |
| V/S | 0.1641 | likely_benign | 0.1548 | benign | -1.322 | Destabilizing | 0.241 | N | 0.529 | neutral | None | None | None | None | N |
| V/T | 0.1403 | likely_benign | 0.1339 | benign | -1.192 | Destabilizing | 0.008 | N | 0.338 | neutral | None | None | None | None | N |
| V/W | 0.7132 | likely_pathogenic | 0.7154 | pathogenic | -0.942 | Destabilizing | 0.981 | D | 0.672 | neutral | None | None | None | None | N |
| V/Y | 0.3936 | ambiguous | 0.3875 | ambiguous | -0.618 | Destabilizing | 0.818 | D | 0.566 | 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.