Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13774 | 41545;41546;41547 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| N2AB | 12133 | 36622;36623;36624 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| N2A | 11206 | 33841;33842;33843 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| N2B | 4709 | 14350;14351;14352 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| Novex-1 | 4834 | 14725;14726;14727 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| Novex-2 | 4901 | 14926;14927;14928 | chr2:178636407;178636406;178636405 | chr2:179501134;179501133;179501132 |
| 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/A | rs1423291544  |
None | 0.052 | N | 0.389 | 0.228 | 0.579595062312 | gnomAD-4.0.0 | 6.89187E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0409E-07 | 0 | 0 |
| V/D | rs1423291544 |
None | 0.484 | N | 0.628 | 0.415 | 0.771676275692 | gnomAD-4.0.0 | 6.89187E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.67068E-05 |
| V/F | rs768582792 |
None | 0.317 | N | 0.438 | 0.112 | 0.589843679045 | gnomAD-4.0.0 | 1.37868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.08156E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs768582792 |
None | 0.004 | N | 0.282 | 0.092 | 0.32471235697 | gnomAD-4.0.0 | 2.06801E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71266E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2131 | likely_benign | 0.2832 | benign | -1.169 | Destabilizing | 0.052 | N | 0.389 | neutral | N | 0.506099526 | None | None | N |
| V/C | 0.767 | likely_pathogenic | 0.8224 | pathogenic | -0.953 | Destabilizing | 0.935 | D | 0.471 | neutral | None | None | None | None | N |
| V/D | 0.5119 | ambiguous | 0.6496 | pathogenic | -1.034 | Destabilizing | 0.484 | N | 0.628 | neutral | N | 0.485742373 | None | None | N |
| V/E | 0.3563 | ambiguous | 0.4443 | ambiguous | -1.009 | Destabilizing | 0.555 | D | 0.576 | neutral | None | None | None | None | N |
| V/F | 0.1545 | likely_benign | 0.2138 | benign | -0.74 | Destabilizing | 0.317 | N | 0.438 | neutral | N | 0.510454987 | None | None | N |
| V/G | 0.431 | ambiguous | 0.5107 | ambiguous | -1.495 | Destabilizing | 0.484 | N | 0.574 | neutral | N | 0.5107927 | None | None | N |
| V/H | 0.4549 | ambiguous | 0.5606 | ambiguous | -0.981 | Destabilizing | 0.935 | D | 0.626 | neutral | None | None | None | None | N |
| V/I | 0.0534 | likely_benign | 0.0586 | benign | -0.377 | Destabilizing | None | N | 0.124 | neutral | N | 0.436360882 | None | None | N |
| V/K | 0.3417 | ambiguous | 0.4307 | ambiguous | -1.189 | Destabilizing | 0.555 | D | 0.578 | neutral | None | None | None | None | N |
| V/L | 0.1226 | likely_benign | 0.1549 | benign | -0.377 | Destabilizing | 0.004 | N | 0.282 | neutral | N | 0.46687838 | None | None | N |
| V/M | 0.1261 | likely_benign | 0.1568 | benign | -0.432 | Destabilizing | 0.38 | N | 0.439 | neutral | None | None | None | None | N |
| V/N | 0.256 | likely_benign | 0.3597 | ambiguous | -1.092 | Destabilizing | 0.791 | D | 0.646 | neutral | None | None | None | None | N |
| V/P | 0.9651 | likely_pathogenic | 0.9765 | pathogenic | -0.605 | Destabilizing | 0.791 | D | 0.601 | neutral | None | None | None | None | N |
| V/Q | 0.3294 | likely_benign | 0.3894 | ambiguous | -1.185 | Destabilizing | 0.791 | D | 0.607 | neutral | None | None | None | None | N |
| V/R | 0.2712 | likely_benign | 0.3632 | ambiguous | -0.717 | Destabilizing | 0.555 | D | 0.639 | neutral | None | None | None | None | N |
| V/S | 0.2452 | likely_benign | 0.3267 | benign | -1.591 | Destabilizing | 0.555 | D | 0.529 | neutral | None | None | None | None | N |
| V/T | 0.1481 | likely_benign | 0.2001 | benign | -1.45 | Destabilizing | 0.149 | N | 0.392 | neutral | None | None | None | None | N |
| V/W | 0.7812 | likely_pathogenic | 0.8471 | pathogenic | -0.972 | Destabilizing | 0.935 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/Y | 0.5117 | ambiguous | 0.6022 | pathogenic | -0.657 | Destabilizing | 0.555 | D | 0.493 | 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.