Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4028 | 12307;12308;12309 | chr2:178741151;178741150;178741149 | chr2:179605878;179605877;179605876 |
| N2AB | 3711 | 11356;11357;11358 | chr2:178741151;178741150;178741149 | chr2:179605878;179605877;179605876 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3665 | 11218;11219;11220 | chr2:178741151;178741150;178741149 | chr2:179605878;179605877;179605876 |
| Novex-1 | 3790 | 11593;11594;11595 | chr2:178741151;178741150;178741149 | chr2:179605878;179605877;179605876 |
| Novex-2 | 3857 | 11794;11795;11796 | chr2:178741151;178741150;178741149 | chr2:179605878;179605877;179605876 |
| 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 | None | None | 0.008 | D | 0.405 | 0.416 | None | 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 |
| V/L | rs773276464  |
-0.938 | 0.349 | D | 0.576 | 0.433 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| V/L | rs773276464 |
-0.938 | 0.349 | D | 0.576 | 0.433 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs773276464 |
-0.938 | 0.349 | D | 0.576 | 0.433 | None | gnomAD-4.0.0 | 7.43723E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32336E-06 | 0 | 1.60102E-05 |
| V/M | rs773276464 |
-0.933 | 0.983 | D | 0.635 | 0.472 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs773276464 |
-0.933 | 0.983 | D | 0.635 | 0.472 | None | gnomAD-4.0.0 | 6.84303E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51965E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6502 | likely_pathogenic | 0.664 | pathogenic | -1.978 | Destabilizing | 0.008 | N | 0.405 | neutral | D | 0.798283987 | None | None | N |
| V/C | 0.8965 | likely_pathogenic | 0.8857 | pathogenic | -1.659 | Destabilizing | 0.989 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/D | 0.9272 | likely_pathogenic | 0.9114 | pathogenic | -2.52 | Highly Destabilizing | 0.011 | N | 0.669 | neutral | None | None | None | None | N |
| V/E | 0.8749 | likely_pathogenic | 0.8717 | pathogenic | -2.447 | Highly Destabilizing | 0.565 | D | 0.714 | prob.delet. | D | 0.797535789 | None | None | N |
| V/F | 0.561 | ambiguous | 0.4595 | ambiguous | -1.37 | Destabilizing | 0.961 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/G | 0.6637 | likely_pathogenic | 0.657 | pathogenic | -2.372 | Highly Destabilizing | 0.565 | D | 0.741 | deleterious | D | 0.797535789 | None | None | N |
| V/H | 0.9542 | likely_pathogenic | 0.9422 | pathogenic | -1.886 | Destabilizing | 0.996 | D | 0.797 | deleterious | None | None | None | None | N |
| V/I | 0.1205 | likely_benign | 0.1282 | benign | -0.943 | Destabilizing | 0.775 | D | 0.557 | neutral | None | None | None | None | N |
| V/K | 0.9334 | likely_pathogenic | 0.924 | pathogenic | -1.69 | Destabilizing | 0.923 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/L | 0.494 | ambiguous | 0.4508 | ambiguous | -0.943 | Destabilizing | 0.349 | N | 0.576 | neutral | D | 0.698486935 | None | None | N |
| V/M | 0.59 | likely_pathogenic | 0.5576 | ambiguous | -0.892 | Destabilizing | 0.983 | D | 0.635 | neutral | D | 0.797755033 | None | None | N |
| V/N | 0.8627 | likely_pathogenic | 0.851 | pathogenic | -1.706 | Destabilizing | 0.923 | D | 0.797 | deleterious | None | None | None | None | N |
| V/P | 0.8347 | likely_pathogenic | 0.8347 | pathogenic | -1.258 | Destabilizing | 0.961 | D | 0.757 | deleterious | None | None | None | None | N |
| V/Q | 0.9052 | likely_pathogenic | 0.8914 | pathogenic | -1.815 | Destabilizing | 0.961 | D | 0.762 | deleterious | None | None | None | None | N |
| V/R | 0.8912 | likely_pathogenic | 0.8645 | pathogenic | -1.207 | Destabilizing | 0.923 | D | 0.798 | deleterious | None | None | None | None | N |
| V/S | 0.7294 | likely_pathogenic | 0.7386 | pathogenic | -2.245 | Highly Destabilizing | 0.633 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/T | 0.7074 | likely_pathogenic | 0.7323 | pathogenic | -2.061 | Highly Destabilizing | 0.775 | D | 0.598 | neutral | None | None | None | None | N |
| V/W | 0.9795 | likely_pathogenic | 0.9689 | pathogenic | -1.676 | Destabilizing | 0.996 | D | 0.767 | deleterious | None | None | None | None | N |
| V/Y | 0.9109 | likely_pathogenic | 0.8772 | pathogenic | -1.394 | Destabilizing | 0.987 | D | 0.705 | prob.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.