Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18486 | 55681;55682;55683 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| N2AB | 16845 | 50758;50759;50760 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| N2A | 15918 | 47977;47978;47979 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| N2B | 9421 | 28486;28487;28488 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| Novex-1 | 9546 | 28861;28862;28863 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| Novex-2 | 9613 | 29062;29063;29064 | chr2:178601541;178601540;178601539 | chr2:179466268;179466267;179466266 |
| 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/P | rs774650474  |
-1.953 | 1.0 | N | 0.885 | 0.617 | 0.810817641556 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| L/P | rs774650474 |
-1.953 | 1.0 | N | 0.885 | 0.617 | 0.810817641556 | gnomAD-4.0.0 | 4.78516E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.31233E-05 | 0 |
| L/V | None | None | 0.999 | N | 0.692 | 0.323 | 0.347879110917 | gnomAD-4.0.0 | 3.19056E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.73233E-06 | 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 | 0.971 | likely_pathogenic | 0.9774 | pathogenic | -2.39 | Highly Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| L/C | 0.8966 | likely_pathogenic | 0.9361 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -2.523 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| L/E | 0.9974 | likely_pathogenic | 0.9981 | pathogenic | -2.337 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/F | 0.3774 | ambiguous | 0.5709 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/G | 0.9935 | likely_pathogenic | 0.9957 | pathogenic | -2.912 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| L/H | 0.9899 | likely_pathogenic | 0.994 | pathogenic | -2.368 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/I | 0.1837 | likely_benign | 0.1997 | benign | -0.905 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| L/K | 0.9925 | likely_pathogenic | 0.995 | pathogenic | -1.769 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/M | 0.2789 | likely_benign | 0.3525 | ambiguous | -0.878 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.508757334 | None | None | N |
| L/N | 0.9962 | likely_pathogenic | 0.9971 | pathogenic | -1.966 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| L/P | 0.9841 | likely_pathogenic | 0.9874 | pathogenic | -1.378 | Destabilizing | 1.0 | D | 0.885 | deleterious | N | 0.483820016 | None | None | N |
| L/Q | 0.9883 | likely_pathogenic | 0.9926 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.888 | deleterious | D | 0.52359636 | None | None | N |
| L/R | 0.9868 | likely_pathogenic | 0.9916 | pathogenic | -1.471 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.541700615 | None | None | N |
| L/S | 0.9956 | likely_pathogenic | 0.997 | pathogenic | -2.671 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| L/T | 0.962 | likely_pathogenic | 0.9718 | pathogenic | -2.343 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/V | 0.2781 | likely_benign | 0.3228 | benign | -1.378 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | N | 0.498418535 | None | None | N |
| L/W | 0.9205 | likely_pathogenic | 0.9699 | pathogenic | -1.762 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/Y | 0.9508 | likely_pathogenic | 0.9781 | pathogenic | -1.475 | Destabilizing | 1.0 | D | 0.849 | 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.