Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16931 | 51016;51017;51018 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| N2AB | 15290 | 46093;46094;46095 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| N2A | 14363 | 43312;43313;43314 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| N2B | 7866 | 23821;23822;23823 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| Novex-1 | 7991 | 24196;24197;24198 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| Novex-2 | 8058 | 24397;24398;24399 | chr2:178611438;178611437;178611436 | chr2:179476165;179476164;179476163 |
| 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/D | rs2056308510  |
None | 0.012 | D | 0.523 | 0.418 | 0.74241836975 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| V/D | rs2056308510 |
None | 0.012 | D | 0.523 | 0.418 | 0.74241836975 | gnomAD-4.0.0 | 5.13007E-06 | None | None | None | None | N | None | 1.69268E-05 | 3.39294E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84835E-05 |
| V/I | None | None | 0.022 | N | 0.141 | 0.138 | 0.508934680445 | gnomAD-4.0.0 | 6.84563E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99782E-07 | 0 | 0 |
| V/L | None | None | 0.454 | N | 0.407 | 0.207 | 0.454426139905 | gnomAD-4.0.0 | 2.05369E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.5884E-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 | 0.5876 | likely_pathogenic | 0.7115 | pathogenic | -2.193 | Highly Destabilizing | 0.625 | D | 0.521 | neutral | D | 0.523038275 | None | None | N |
| V/C | 0.8723 | likely_pathogenic | 0.9206 | pathogenic | -1.765 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| V/D | 0.9563 | likely_pathogenic | 0.976 | pathogenic | -2.939 | Highly Destabilizing | 0.012 | N | 0.523 | neutral | D | 0.622313541 | None | None | N |
| V/E | 0.7699 | likely_pathogenic | 0.8551 | pathogenic | -2.763 | Highly Destabilizing | 0.728 | D | 0.638 | neutral | None | None | None | None | N |
| V/F | 0.4742 | ambiguous | 0.569 | pathogenic | -1.349 | Destabilizing | 0.012 | N | 0.412 | neutral | D | 0.560358386 | None | None | N |
| V/G | 0.7625 | likely_pathogenic | 0.8774 | pathogenic | -2.676 | Highly Destabilizing | 0.801 | D | 0.678 | prob.neutral | D | 0.588814847 | None | None | N |
| V/H | 0.94 | likely_pathogenic | 0.9681 | pathogenic | -2.406 | Highly Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| V/I | 0.0848 | likely_benign | 0.0916 | benign | -0.855 | Destabilizing | 0.022 | N | 0.141 | neutral | N | 0.475097212 | None | None | N |
| V/K | 0.8587 | likely_pathogenic | 0.9164 | pathogenic | -1.815 | Destabilizing | 0.949 | D | 0.634 | neutral | None | None | None | None | N |
| V/L | 0.3809 | ambiguous | 0.4956 | ambiguous | -0.855 | Destabilizing | 0.454 | N | 0.407 | neutral | N | 0.519471313 | None | None | N |
| V/M | 0.2715 | likely_benign | 0.3168 | benign | -0.881 | Destabilizing | 0.974 | D | 0.573 | neutral | None | None | None | None | N |
| V/N | 0.8742 | likely_pathogenic | 0.9267 | pathogenic | -2.067 | Highly Destabilizing | 0.904 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/P | 0.9934 | likely_pathogenic | 0.997 | pathogenic | -1.275 | Destabilizing | 0.974 | D | 0.632 | neutral | None | None | None | None | N |
| V/Q | 0.7279 | likely_pathogenic | 0.8432 | pathogenic | -1.976 | Destabilizing | 0.974 | D | 0.636 | neutral | None | None | None | None | N |
| V/R | 0.8274 | likely_pathogenic | 0.9036 | pathogenic | -1.55 | Destabilizing | 0.974 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/S | 0.7299 | likely_pathogenic | 0.8153 | pathogenic | -2.624 | Highly Destabilizing | 0.842 | D | 0.641 | neutral | None | None | None | None | N |
| V/T | 0.5535 | ambiguous | 0.6507 | pathogenic | -2.326 | Highly Destabilizing | 0.842 | D | 0.582 | neutral | None | None | None | None | N |
| V/W | 0.97 | likely_pathogenic | 0.9849 | pathogenic | -1.877 | Destabilizing | 0.998 | D | 0.69 | prob.neutral | None | None | None | None | N |
| V/Y | 0.8863 | likely_pathogenic | 0.9356 | pathogenic | -1.554 | Destabilizing | 0.904 | D | 0.637 | 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.