Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18775 | 56548;56549;56550 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| N2AB | 17134 | 51625;51626;51627 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| N2A | 16207 | 48844;48845;48846 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| N2B | 9710 | 29353;29354;29355 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| Novex-1 | 9835 | 29728;29729;29730 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| Novex-2 | 9902 | 29929;29930;29931 | chr2:178599578;178599577;178599576 | chr2:179464305;179464304;179464303 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs1330261785  |
0.303 | 0.999 | N | 0.646 | 0.449 | 0.49908893446 | gnomAD-2.1.1 | 4.28E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.34E-06 | 0 |
| K/E | rs1330261785 |
0.303 | 0.999 | N | 0.646 | 0.449 | 0.49908893446 | gnomAD-4.0.0 | 3.30844E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93067E-06 | 0 | 0 |
| K/N | rs747785028 |
-0.295 | 1.0 | D | 0.799 | 0.401 | 0.415564226483 | gnomAD-2.1.1 | 8.6E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.88E-05 | 0 |
| K/N | rs747785028 |
-0.295 | 1.0 | D | 0.799 | 0.401 | 0.415564226483 | gnomAD-4.0.0 | 2.78477E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.73077E-06 | 0 | 1.68674E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3878 | ambiguous | 0.3464 | ambiguous | -0.651 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| K/C | 0.6857 | likely_pathogenic | 0.6421 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| K/D | 0.8252 | likely_pathogenic | 0.7776 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| K/E | 0.2281 | likely_benign | 0.1911 | benign | -0.235 | Destabilizing | 0.999 | D | 0.646 | neutral | N | 0.490189461 | None | None | I |
| K/F | 0.9159 | likely_pathogenic | 0.8877 | pathogenic | -0.134 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | I |
| K/G | 0.5839 | likely_pathogenic | 0.5002 | ambiguous | -1.066 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| K/H | 0.4829 | ambiguous | 0.4244 | ambiguous | -1.412 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| K/I | 0.6242 | likely_pathogenic | 0.5902 | pathogenic | 0.449 | Stabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | I |
| K/L | 0.6078 | likely_pathogenic | 0.5561 | ambiguous | 0.449 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| K/M | 0.3797 | ambiguous | 0.3241 | benign | 0.22 | Stabilizing | 1.0 | D | 0.834 | deleterious | N | 0.492217378 | None | None | I |
| K/N | 0.6948 | likely_pathogenic | 0.6258 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.526480288 | None | None | I |
| K/P | 0.9824 | likely_pathogenic | 0.9766 | pathogenic | 0.113 | Stabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| K/Q | 0.1614 | likely_benign | 0.1422 | benign | -0.738 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.529539236 | None | None | I |
| K/R | 0.0935 | likely_benign | 0.0899 | benign | -0.904 | Destabilizing | 0.999 | D | 0.595 | neutral | D | 0.531598107 | None | None | I |
| K/S | 0.5478 | ambiguous | 0.4806 | ambiguous | -1.389 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | I |
| K/T | 0.2819 | likely_benign | 0.2474 | benign | -1.018 | Destabilizing | 1.0 | D | 0.818 | deleterious | N | 0.490519488 | None | None | I |
| K/V | 0.4584 | ambiguous | 0.4289 | ambiguous | 0.113 | Stabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | I |
| K/W | 0.9071 | likely_pathogenic | 0.8666 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| K/Y | 0.8328 | likely_pathogenic | 0.7768 | pathogenic | 0.238 | Stabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | I |
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.