Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1562 | 4909;4910;4911 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| N2AB | 1562 | 4909;4910;4911 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| N2A | 1562 | 4909;4910;4911 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| N2B | 1516 | 4771;4772;4773 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| Novex-1 | 1516 | 4771;4772;4773 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| Novex-2 | 1516 | 4771;4772;4773 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
| Novex-3 | 1562 | 4909;4910;4911 | chr2:178777279;178777278;178777277 | chr2:179642006;179642005;179642004 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | None | None | 1.0 | N | 0.752 | 0.257 | 0.487277728379 | gnomAD-4.0.0 | 1.59087E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77577E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs562318663  |
None | 1.0 | N | 0.869 | 0.568 | 0.636100073078 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85688E-06 | 0 | 0 |
| L/V | rs1221271314 |
-1.514 | 0.999 | D | 0.519 | 0.224 | 0.555595671355 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1221271314 |
-1.514 | 0.999 | D | 0.519 | 0.224 | 0.555595671355 | gnomAD-4.0.0 | 1.59087E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77577E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9329 | likely_pathogenic | 0.9221 | pathogenic | -2.057 | Highly Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/C | 0.9539 | likely_pathogenic | 0.9427 | pathogenic | -1.252 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| L/D | 0.9988 | likely_pathogenic | 0.9986 | pathogenic | -1.455 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/E | 0.9917 | likely_pathogenic | 0.9891 | pathogenic | -1.37 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/F | 0.7832 | likely_pathogenic | 0.7227 | pathogenic | -1.297 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/G | 0.9858 | likely_pathogenic | 0.9833 | pathogenic | -2.482 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| L/H | 0.9859 | likely_pathogenic | 0.9814 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/I | 0.3771 | ambiguous | 0.3291 | benign | -0.908 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | N |
| L/K | 0.9879 | likely_pathogenic | 0.9834 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| L/M | 0.368 | ambiguous | 0.3087 | benign | -0.716 | Destabilizing | 1.0 | D | 0.752 | deleterious | N | 0.519431912 | None | None | N |
| L/N | 0.9912 | likely_pathogenic | 0.9892 | pathogenic | -1.324 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/P | 0.8438 | likely_pathogenic | 0.8789 | pathogenic | -1.263 | Destabilizing | 1.0 | D | 0.869 | deleterious | N | 0.44225729 | None | None | N |
| L/Q | 0.9673 | likely_pathogenic | 0.9524 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.5937614 | None | None | N |
| L/R | 0.9797 | likely_pathogenic | 0.973 | pathogenic | -0.924 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.569866561 | None | None | N |
| L/S | 0.9906 | likely_pathogenic | 0.9875 | pathogenic | -2.049 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/T | 0.9622 | likely_pathogenic | 0.9534 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| L/V | 0.492 | ambiguous | 0.4411 | ambiguous | -1.263 | Destabilizing | 0.999 | D | 0.519 | neutral | D | 0.567833314 | None | None | N |
| L/W | 0.9564 | likely_pathogenic | 0.9383 | pathogenic | -1.447 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| L/Y | 0.98 | likely_pathogenic | 0.9716 | pathogenic | -1.213 | Destabilizing | 1.0 | D | 0.85 | 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.