Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27636 | 83131;83132;83133 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| N2AB | 25995 | 78208;78209;78210 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| N2A | 25068 | 75427;75428;75429 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| N2B | 18571 | 55936;55937;55938 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| Novex-1 | 18696 | 56311;56312;56313 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| Novex-2 | 18763 | 56512;56513;56514 | chr2:178563226;178563225;178563224 | chr2:179427953;179427952;179427951 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 1.0 | D | 0.871 | 0.769 | 0.827322877922 | gnomAD-4.0.0 | 6.84237E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99518E-07 | 0 | 0 |
| L/I | None | None | 0.999 | D | 0.83 | 0.73 | 0.777571993627 | gnomAD-4.0.0 | 6.84237E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99518E-07 | 0 | 0 |
| L/V | rs1319880054  |
-1.641 | 0.999 | D | 0.837 | 0.757 | 0.778580615627 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/V | rs1319880054 |
-1.641 | 0.999 | D | 0.837 | 0.757 | 0.778580615627 | gnomAD-4.0.0 | 6.84237E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-05 | 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 | 0.9653 | likely_pathogenic | 0.953 | pathogenic | -2.522 | Highly Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| L/C | 0.9546 | likely_pathogenic | 0.9411 | pathogenic | -2.34 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9988 | pathogenic | -2.154 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/E | 0.9934 | likely_pathogenic | 0.9907 | pathogenic | -1.984 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/F | 0.8373 | likely_pathogenic | 0.8087 | pathogenic | -1.799 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.6429206 | None | None | N |
| L/G | 0.9911 | likely_pathogenic | 0.9867 | pathogenic | -3.012 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/H | 0.9916 | likely_pathogenic | 0.988 | pathogenic | -2.285 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.675998703 | None | None | N |
| L/I | 0.3301 | likely_benign | 0.293 | benign | -1.137 | Destabilizing | 0.999 | D | 0.83 | deleterious | D | 0.632624992 | None | None | N |
| L/K | 0.9896 | likely_pathogenic | 0.9862 | pathogenic | -1.788 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/M | 0.4173 | ambiguous | 0.3856 | ambiguous | -1.262 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/N | 0.9937 | likely_pathogenic | 0.9905 | pathogenic | -1.999 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/P | 0.9912 | likely_pathogenic | 0.9873 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.833 | deleterious | D | 0.675998703 | None | None | N |
| L/Q | 0.9762 | likely_pathogenic | 0.9671 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/R | 0.9797 | likely_pathogenic | 0.9731 | pathogenic | -1.409 | Destabilizing | 1.0 | D | 0.838 | deleterious | D | 0.659747178 | None | None | N |
| L/S | 0.9955 | likely_pathogenic | 0.9928 | pathogenic | -2.845 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/T | 0.9727 | likely_pathogenic | 0.9615 | pathogenic | -2.519 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/V | 0.4254 | ambiguous | 0.3714 | ambiguous | -1.577 | Destabilizing | 0.999 | D | 0.837 | deleterious | D | 0.597678853 | None | None | N |
| L/W | 0.9718 | likely_pathogenic | 0.9605 | pathogenic | -1.951 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| L/Y | 0.9811 | likely_pathogenic | 0.9735 | pathogenic | -1.702 | Destabilizing | 1.0 | D | 0.825 | 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.