Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17095 | 51508;51509;51510 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| N2AB | 15454 | 46585;46586;46587 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| N2A | 14527 | 43804;43805;43806 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| N2B | 8030 | 24313;24314;24315 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| Novex-1 | 8155 | 24688;24689;24690 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| Novex-2 | 8222 | 24889;24890;24891 | chr2:178610243;178610242;178610241 | chr2:179474970;179474969;179474968 |
| 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/K | rs878877393  |
None | 0.934 | N | 0.409 | 0.392 | 0.712297760019 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| I/T | None | None | 0.051 | N | 0.253 | 0.207 | 0.590758969589 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 3.66327E-05 |
| I/V | None | None | 0.022 | N | 0.117 | 0.057 | 0.346315397577 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7764 | likely_pathogenic | 0.8003 | pathogenic | -1.25 | Destabilizing | 0.525 | D | 0.394 | neutral | None | None | None | None | I |
| I/C | 0.9172 | likely_pathogenic | 0.9335 | pathogenic | -0.716 | Destabilizing | 0.998 | D | 0.373 | neutral | None | None | None | None | I |
| I/D | 0.972 | likely_pathogenic | 0.9754 | pathogenic | -0.755 | Destabilizing | 0.949 | D | 0.429 | neutral | None | None | None | None | I |
| I/E | 0.9308 | likely_pathogenic | 0.9352 | pathogenic | -0.768 | Destabilizing | 0.949 | D | 0.414 | neutral | None | None | None | None | I |
| I/F | 0.4308 | ambiguous | 0.4442 | ambiguous | -0.81 | Destabilizing | 0.974 | D | 0.379 | neutral | None | None | None | None | I |
| I/G | 0.9426 | likely_pathogenic | 0.9445 | pathogenic | -1.532 | Destabilizing | 0.842 | D | 0.394 | neutral | None | None | None | None | I |
| I/H | 0.8642 | likely_pathogenic | 0.8797 | pathogenic | -0.68 | Destabilizing | 0.998 | D | 0.433 | neutral | None | None | None | None | I |
| I/K | 0.8744 | likely_pathogenic | 0.881 | pathogenic | -0.875 | Destabilizing | 0.934 | D | 0.409 | neutral | N | 0.425395282 | None | None | I |
| I/L | 0.2049 | likely_benign | 0.219 | benign | -0.572 | Destabilizing | 0.267 | N | 0.201 | neutral | N | 0.406676236 | None | None | I |
| I/M | 0.2209 | likely_benign | 0.2466 | benign | -0.502 | Destabilizing | 0.966 | D | 0.437 | neutral | N | 0.423955275 | None | None | I |
| I/N | 0.6561 | likely_pathogenic | 0.7124 | pathogenic | -0.725 | Destabilizing | 0.949 | D | 0.437 | neutral | None | None | None | None | I |
| I/P | 0.9863 | likely_pathogenic | 0.9862 | pathogenic | -0.766 | Destabilizing | 0.974 | D | 0.435 | neutral | None | None | None | None | I |
| I/Q | 0.7969 | likely_pathogenic | 0.8166 | pathogenic | -0.902 | Destabilizing | 0.974 | D | 0.43 | neutral | None | None | None | None | I |
| I/R | 0.8367 | likely_pathogenic | 0.8387 | pathogenic | -0.265 | Destabilizing | 0.966 | D | 0.441 | neutral | N | 0.418528025 | None | None | I |
| I/S | 0.659 | likely_pathogenic | 0.7034 | pathogenic | -1.256 | Destabilizing | 0.728 | D | 0.338 | neutral | None | None | None | None | I |
| I/T | 0.577 | likely_pathogenic | 0.6381 | pathogenic | -1.161 | Destabilizing | 0.051 | N | 0.253 | neutral | N | 0.382433939 | None | None | I |
| I/V | 0.1706 | likely_benign | 0.173 | benign | -0.766 | Destabilizing | 0.022 | N | 0.117 | neutral | N | 0.383799376 | None | None | I |
| I/W | 0.9484 | likely_pathogenic | 0.9553 | pathogenic | -0.885 | Destabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | I |
| I/Y | 0.811 | likely_pathogenic | 0.8419 | pathogenic | -0.657 | Destabilizing | 0.991 | D | 0.406 | 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.