Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17062 | 51409;51410;51411 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| N2AB | 15421 | 46486;46487;46488 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| N2A | 14494 | 43705;43706;43707 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| N2B | 7997 | 24214;24215;24216 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| Novex-1 | 8122 | 24589;24590;24591 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| Novex-2 | 8189 | 24790;24791;24792 | chr2:178610342;178610341;178610340 | chr2:179475069;179475068;179475067 |
| 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/N | rs876658064  |
-0.208 | None | N | 0.081 | 0.068 | 0.0806252709748 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 2.29516E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs876658064 |
-0.208 | None | N | 0.081 | 0.068 | 0.0806252709748 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44809E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs876658064 |
-0.208 | None | N | 0.081 | 0.068 | 0.0806252709748 | gnomAD-4.0.0 | 6.20084E-06 | None | None | None | None | N | None | 1.20257E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48037E-07 | 0 | 0 |
| S/R | rs2154198973 |
None | 0.497 | N | 0.461 | 0.267 | 0.283761946502 | gnomAD-4.0.0 | 4.78051E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.30095E-05 | 0 |
| S/T | rs876658064 |
None | 0.001 | N | 0.177 | 0.054 | 0.0716867268079 | gnomAD-4.0.0 | 3.42312E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49948E-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 | 0.0978 | likely_benign | 0.1063 | benign | -0.614 | Destabilizing | 0.072 | N | 0.453 | neutral | None | None | None | None | N |
| S/C | 0.1885 | likely_benign | 0.1827 | benign | -0.572 | Destabilizing | 0.883 | D | 0.49 | neutral | D | 0.588606063 | None | None | N |
| S/D | 0.53 | ambiguous | 0.5667 | pathogenic | -0.908 | Destabilizing | 0.157 | N | 0.428 | neutral | None | None | None | None | N |
| S/E | 0.678 | likely_pathogenic | 0.714 | pathogenic | -0.951 | Destabilizing | 0.272 | N | 0.414 | neutral | None | None | None | None | N |
| S/F | 0.2819 | likely_benign | 0.2904 | benign | -1.167 | Destabilizing | 0.726 | D | 0.557 | neutral | None | None | None | None | N |
| S/G | 0.0991 | likely_benign | 0.0999 | benign | -0.771 | Destabilizing | 0.055 | N | 0.42 | neutral | N | 0.483601672 | None | None | N |
| S/H | 0.4041 | ambiguous | 0.4187 | ambiguous | -1.394 | Destabilizing | 0.567 | D | 0.487 | neutral | None | None | None | None | N |
| S/I | 0.2723 | likely_benign | 0.3191 | benign | -0.31 | Destabilizing | 0.331 | N | 0.557 | neutral | D | 0.587059405 | None | None | N |
| S/K | 0.8472 | likely_pathogenic | 0.8663 | pathogenic | -0.679 | Destabilizing | 0.157 | N | 0.43 | neutral | None | None | None | None | N |
| S/L | 0.1475 | likely_benign | 0.1557 | benign | -0.31 | Destabilizing | 0.157 | N | 0.49 | neutral | None | None | None | None | N |
| S/M | 0.1728 | likely_benign | 0.1978 | benign | 0.185 | Stabilizing | 0.909 | D | 0.481 | neutral | None | None | None | None | N |
| S/N | 0.1004 | likely_benign | 0.1056 | benign | -0.683 | Destabilizing | None | N | 0.081 | neutral | N | 0.443067937 | None | None | N |
| S/P | 0.901 | likely_pathogenic | 0.9137 | pathogenic | -0.383 | Destabilizing | 0.726 | D | 0.49 | neutral | None | None | None | None | N |
| S/Q | 0.5492 | ambiguous | 0.5744 | pathogenic | -1.029 | Destabilizing | 0.567 | D | 0.489 | neutral | None | None | None | None | N |
| S/R | 0.857 | likely_pathogenic | 0.861 | pathogenic | -0.444 | Destabilizing | 0.497 | N | 0.461 | neutral | N | 0.479158969 | None | None | N |
| S/T | 0.0707 | likely_benign | 0.0801 | benign | -0.66 | Destabilizing | 0.001 | N | 0.177 | neutral | N | 0.443432331 | None | None | N |
| S/V | 0.2539 | likely_benign | 0.2956 | benign | -0.383 | Destabilizing | 0.396 | N | 0.493 | neutral | None | None | None | None | N |
| S/W | 0.6067 | likely_pathogenic | 0.6047 | pathogenic | -1.157 | Destabilizing | 0.968 | D | 0.667 | neutral | None | None | None | None | N |
| S/Y | 0.2643 | likely_benign | 0.2762 | benign | -0.85 | Destabilizing | 0.726 | D | 0.561 | 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.