Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21339 | 64240;64241;64242 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| N2AB | 19698 | 59317;59318;59319 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| N2A | 18771 | 56536;56537;56538 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| N2B | 12274 | 37045;37046;37047 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| Novex-1 | 12399 | 37420;37421;37422 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| Novex-2 | 12466 | 37621;37622;37623 | chr2:178587196;178587195;178587194 | chr2:179451923;179451922;179451921 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1357840635  |
-2.352 | 1.0 | D | 0.726 | 0.634 | 0.673162676466 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1357840635 |
-2.352 | 1.0 | D | 0.726 | 0.634 | 0.673162676466 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs1357840635 |
-2.352 | 1.0 | D | 0.726 | 0.634 | 0.673162676466 | gnomAD-4.0.0 | 6.57644E-06 | None | None | None | None | N | None | 2.41348E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.968 | likely_pathogenic | 0.9635 | pathogenic | -1.722 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| R/C | 0.5444 | ambiguous | 0.5614 | ambiguous | -1.759 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/D | 0.9973 | likely_pathogenic | 0.9977 | pathogenic | -0.894 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/E | 0.9597 | likely_pathogenic | 0.9623 | pathogenic | -0.701 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | N |
| R/F | 0.9865 | likely_pathogenic | 0.9895 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9483 | likely_pathogenic | 0.9477 | pathogenic | -2.055 | Highly Destabilizing | 1.0 | D | 0.726 | prob.delet. | D | 0.548388296 | None | None | N |
| R/H | 0.3886 | ambiguous | 0.4064 | ambiguous | -2.032 | Highly Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| R/I | 0.9567 | likely_pathogenic | 0.9637 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.828 | deleterious | N | 0.514154796 | None | None | N |
| R/K | 0.3866 | ambiguous | 0.4056 | ambiguous | -1.393 | Destabilizing | 0.997 | D | 0.635 | neutral | N | 0.482564187 | None | None | N |
| R/L | 0.913 | likely_pathogenic | 0.9251 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/M | 0.9392 | likely_pathogenic | 0.9477 | pathogenic | -1.246 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/N | 0.9874 | likely_pathogenic | 0.9883 | pathogenic | -1.241 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/P | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -1.075 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/Q | 0.3874 | ambiguous | 0.3864 | ambiguous | -1.142 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/S | 0.9722 | likely_pathogenic | 0.9692 | pathogenic | -2.068 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.502959393 | None | None | N |
| R/T | 0.9625 | likely_pathogenic | 0.9591 | pathogenic | -1.675 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.496642744 | None | None | N |
| R/V | 0.9648 | likely_pathogenic | 0.9696 | pathogenic | -1.075 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/W | 0.84 | likely_pathogenic | 0.8745 | pathogenic | -0.689 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/Y | 0.9575 | likely_pathogenic | 0.9676 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.828 | deleterious | 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.