Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22007 | 66244;66245;66246 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| N2AB | 20366 | 61321;61322;61323 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| N2A | 19439 | 58540;58541;58542 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| N2B | 12942 | 39049;39050;39051 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| Novex-1 | 13067 | 39424;39425;39426 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| Novex-2 | 13134 | 39625;39626;39627 | chr2:178582437;178582436;178582435 | chr2:179447164;179447163;179447162 |
| 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/A | None | None | 0.454 | N | 0.296 | 0.136 | 0.236278675362 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/F | rs1433594102  |
-0.717 | 0.966 | N | 0.551 | 0.342 | 0.629760217842 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/F | rs1433594102 |
-0.717 | 0.966 | N | 0.551 | 0.342 | 0.629760217842 | gnomAD-4.0.0 | 1.5931E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1206 | likely_benign | 0.1359 | benign | -0.455 | Destabilizing | 0.454 | N | 0.296 | neutral | N | 0.437193931 | None | None | N |
| S/C | 0.162 | likely_benign | 0.1718 | benign | -0.422 | Destabilizing | 0.997 | D | 0.445 | neutral | N | 0.480931572 | None | None | N |
| S/D | 0.7123 | likely_pathogenic | 0.7337 | pathogenic | -0.272 | Destabilizing | 0.842 | D | 0.417 | neutral | None | None | None | None | N |
| S/E | 0.8039 | likely_pathogenic | 0.8361 | pathogenic | -0.305 | Destabilizing | 0.842 | D | 0.429 | neutral | None | None | None | None | N |
| S/F | 0.4766 | ambiguous | 0.5027 | ambiguous | -0.687 | Destabilizing | 0.966 | D | 0.551 | neutral | N | 0.47192867 | None | None | N |
| S/G | 0.2048 | likely_benign | 0.2115 | benign | -0.676 | Destabilizing | 0.688 | D | 0.419 | neutral | None | None | None | None | N |
| S/H | 0.6194 | likely_pathogenic | 0.65 | pathogenic | -1.199 | Destabilizing | 0.998 | D | 0.447 | neutral | None | None | None | None | N |
| S/I | 0.4787 | ambiguous | 0.5077 | ambiguous | 0.012 | Stabilizing | 0.949 | D | 0.518 | neutral | None | None | None | None | N |
| S/K | 0.898 | likely_pathogenic | 0.9219 | pathogenic | -0.784 | Destabilizing | 0.842 | D | 0.423 | neutral | None | None | None | None | N |
| S/L | 0.1729 | likely_benign | 0.1875 | benign | 0.012 | Stabilizing | 0.728 | D | 0.454 | neutral | None | None | None | None | N |
| S/M | 0.2616 | likely_benign | 0.2852 | benign | 0.227 | Stabilizing | 0.991 | D | 0.456 | neutral | None | None | None | None | N |
| S/N | 0.3178 | likely_benign | 0.3094 | benign | -0.666 | Destabilizing | 0.842 | D | 0.449 | neutral | None | None | None | None | N |
| S/P | 0.966 | likely_pathogenic | 0.9707 | pathogenic | -0.11 | Destabilizing | 0.012 | N | 0.243 | neutral | N | 0.513865203 | None | None | N |
| S/Q | 0.7433 | likely_pathogenic | 0.768 | pathogenic | -0.847 | Destabilizing | 0.974 | D | 0.471 | neutral | None | None | None | None | N |
| S/R | 0.8774 | likely_pathogenic | 0.9069 | pathogenic | -0.614 | Destabilizing | 0.949 | D | 0.463 | neutral | None | None | None | None | N |
| S/T | 0.0849 | likely_benign | 0.0906 | benign | -0.669 | Destabilizing | 0.007 | N | 0.13 | neutral | N | 0.442596963 | None | None | N |
| S/V | 0.3933 | ambiguous | 0.4206 | ambiguous | -0.11 | Destabilizing | 0.728 | D | 0.469 | neutral | None | None | None | None | N |
| S/W | 0.6652 | likely_pathogenic | 0.6998 | pathogenic | -0.698 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| S/Y | 0.4162 | ambiguous | 0.4401 | ambiguous | -0.435 | Destabilizing | 0.989 | D | 0.533 | neutral | N | 0.501456053 | 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.