Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1465 | 4618;4619;4620 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| N2AB | 1465 | 4618;4619;4620 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| N2A | 1465 | 4618;4619;4620 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| N2B | 1419 | 4480;4481;4482 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| Novex-1 | 1419 | 4480;4481;4482 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| Novex-2 | 1419 | 4480;4481;4482 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
| Novex-3 | 1465 | 4618;4619;4620 | chr2:178777791;178777790;178777789 | chr2:179642518;179642517;179642516 |
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/Y | rs2092386112  |
None | 0.999 | D | 0.575 | 0.669 | 0.849710504893 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | rs2092386112 |
None | 0.999 | D | 0.575 | 0.669 | 0.849710504893 | gnomAD-4.0.0 | 6.57194E-06 | None | None | None | None | I | None | 0 | 6.54707E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1519 | likely_benign | 0.1599 | benign | -0.263 | Destabilizing | 0.973 | D | 0.373 | neutral | D | 0.599397884 | None | None | I |
| S/C | 0.4062 | ambiguous | 0.3979 | ambiguous | -0.421 | Destabilizing | 1.0 | D | 0.535 | neutral | D | 0.695645667 | None | None | I |
| S/D | 0.6453 | likely_pathogenic | 0.6495 | pathogenic | 0.456 | Stabilizing | 0.996 | D | 0.435 | neutral | None | None | None | None | I |
| S/E | 0.9064 | likely_pathogenic | 0.9021 | pathogenic | 0.436 | Stabilizing | 0.996 | D | 0.423 | neutral | None | None | None | None | I |
| S/F | 0.7647 | likely_pathogenic | 0.7468 | pathogenic | -0.76 | Destabilizing | 0.999 | D | 0.577 | neutral | D | 0.695897715 | None | None | I |
| S/G | 0.1688 | likely_benign | 0.1748 | benign | -0.431 | Destabilizing | 0.996 | D | 0.354 | neutral | None | None | None | None | I |
| S/H | 0.7907 | likely_pathogenic | 0.7795 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | I |
| S/I | 0.7088 | likely_pathogenic | 0.7006 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.576 | neutral | None | None | None | None | I |
| S/K | 0.9715 | likely_pathogenic | 0.97 | pathogenic | -0.188 | Destabilizing | 0.996 | D | 0.435 | neutral | None | None | None | None | I |
| S/L | 0.4122 | ambiguous | 0.3962 | ambiguous | 0.059 | Stabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | I |
| S/M | 0.6556 | likely_pathogenic | 0.6481 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.523 | neutral | None | None | None | None | I |
| S/N | 0.2433 | likely_benign | 0.2437 | benign | -0.249 | Destabilizing | 0.999 | D | 0.459 | neutral | None | None | None | None | I |
| S/P | 0.221 | likely_benign | 0.229 | benign | -0.016 | Destabilizing | 0.217 | N | 0.289 | neutral | D | 0.529589149 | None | None | I |
| S/Q | 0.8864 | likely_pathogenic | 0.8792 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.507 | neutral | None | None | None | None | I |
| S/R | 0.9468 | likely_pathogenic | 0.9409 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | I |
| S/T | 0.1739 | likely_benign | 0.1781 | benign | -0.262 | Destabilizing | 0.994 | D | 0.377 | neutral | D | 0.556524778 | None | None | I |
| S/V | 0.6558 | likely_pathogenic | 0.6551 | pathogenic | -0.016 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | I |
| S/W | 0.8874 | likely_pathogenic | 0.871 | pathogenic | -0.861 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| S/Y | 0.6926 | likely_pathogenic | 0.6698 | pathogenic | -0.494 | Destabilizing | 0.999 | D | 0.575 | neutral | D | 0.695826244 | 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.