Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26225 | 78898;78899;78900 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| N2AB | 24584 | 73975;73976;73977 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| N2A | 23657 | 71194;71195;71196 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| N2B | 17160 | 51703;51704;51705 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| Novex-1 | 17285 | 52078;52079;52080 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| Novex-2 | 17352 | 52279;52280;52281 | chr2:178567459;178567458;178567457 | chr2:179432186;179432185;179432184 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.164 | N | 0.429 | 0.34 | 0.418344901717 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 0 | 0 |
| I/N | None | None | 0.979 | D | 0.802 | 0.752 | 0.877426635404 | gnomAD-4.0.0 | 6.8458E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99776E-07 | 0 | 0 |
| I/T | rs12463674  |
-1.944 | 0.684 | N | 0.651 | 0.438 | None | gnomAD-2.1.1 | 2.34287E-01 | None | None | None | None | N | None | 4.86473E-02 | 1.11736E-01 | None | 2.0979E-01 | 4.55621E-02 | None | 2.20055E-01 | None | 3.83921E-01 | 3.0754E-01 | 2.45344E-01 |
| I/T | rs12463674 |
-1.944 | 0.684 | N | 0.651 | 0.438 | None | gnomAD-3.1.2 | 2.14052E-01 | None | None | None | None | N | None | 5.38053E-02 | 1.52639E-01 | 2.2467E-01 | 2.10208E-01 | 5.20712E-02 | None | 3.86338E-01 | 2.40506E-01 | 3.10594E-01 | 2.24502E-01 | 2.02586E-01 |
| I/T | rs12463674 |
-1.944 | 0.684 | N | 0.651 | 0.438 | None | 1000 genomes | 1.29992E-01 | None | None | None | None | N | None | 5.3E-03 | 1.124E-01 | None | None | 4.27E-02 | 3.091E-01 | None | None | None | 2.168E-01 | None |
| I/T | rs12463674 |
-1.944 | 0.684 | N | 0.651 | 0.438 | None | gnomAD-4.0.0 | 2.78864E-01 | None | None | None | None | N | None | 4.83118E-02 | 1.22988E-01 | None | 2.11636E-01 | 4.99732E-02 | None | 3.79029E-01 | 2.10152E-01 | 3.12313E-01 | 2.23054E-01 | 2.5571E-01 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3971 | ambiguous | 0.3563 | ambiguous | -2.137 | Highly Destabilizing | 0.016 | N | 0.431 | neutral | None | None | None | None | N |
| I/C | 0.8146 | likely_pathogenic | 0.7824 | pathogenic | -1.303 | Destabilizing | 0.984 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/D | 0.9791 | likely_pathogenic | 0.9731 | pathogenic | -1.777 | Destabilizing | 0.953 | D | 0.78 | deleterious | None | None | None | None | N |
| I/E | 0.9373 | likely_pathogenic | 0.9231 | pathogenic | -1.706 | Destabilizing | 0.854 | D | 0.779 | deleterious | None | None | None | None | N |
| I/F | 0.3889 | ambiguous | 0.3606 | ambiguous | -1.449 | Destabilizing | 0.884 | D | 0.671 | neutral | N | 0.50478236 | None | None | N |
| I/G | 0.9015 | likely_pathogenic | 0.8711 | pathogenic | -2.554 | Highly Destabilizing | 0.742 | D | 0.766 | deleterious | None | None | None | None | N |
| I/H | 0.9245 | likely_pathogenic | 0.9019 | pathogenic | -1.861 | Destabilizing | 0.996 | D | 0.807 | deleterious | None | None | None | None | N |
| I/K | 0.8371 | likely_pathogenic | 0.7946 | pathogenic | -1.532 | Destabilizing | 0.854 | D | 0.767 | deleterious | None | None | None | None | N |
| I/L | 0.1715 | likely_benign | 0.1586 | benign | -1.011 | Destabilizing | 0.164 | N | 0.405 | neutral | N | 0.494373879 | None | None | N |
| I/M | 0.1159 | likely_benign | 0.1026 | benign | -0.743 | Destabilizing | 0.164 | N | 0.429 | neutral | N | 0.511392178 | None | None | N |
| I/N | 0.835 | likely_pathogenic | 0.7946 | pathogenic | -1.413 | Destabilizing | 0.979 | D | 0.802 | deleterious | D | 0.544157648 | None | None | N |
| I/P | 0.9141 | likely_pathogenic | 0.8864 | pathogenic | -1.359 | Destabilizing | 0.953 | D | 0.781 | deleterious | None | None | None | None | N |
| I/Q | 0.8674 | likely_pathogenic | 0.831 | pathogenic | -1.508 | Destabilizing | 0.953 | D | 0.809 | deleterious | None | None | None | None | N |
| I/R | 0.7749 | likely_pathogenic | 0.7264 | pathogenic | -1.008 | Destabilizing | 0.953 | D | 0.796 | deleterious | None | None | None | None | N |
| I/S | 0.624 | likely_pathogenic | 0.5732 | pathogenic | -2.086 | Highly Destabilizing | 0.521 | D | 0.711 | prob.delet. | D | 0.525799903 | None | None | N |
| I/T | 0.2306 | likely_benign | 0.1671 | benign | -1.887 | Destabilizing | 0.684 | D | 0.651 | neutral | N | 0.504808813 | None | None | N |
| I/V | 0.0701 | likely_benign | 0.0687 | benign | -1.359 | Destabilizing | 0.003 | N | 0.219 | neutral | N | 0.435060489 | None | None | N |
| I/W | 0.9311 | likely_pathogenic | 0.9098 | pathogenic | -1.629 | Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| I/Y | 0.8514 | likely_pathogenic | 0.8268 | pathogenic | -1.401 | Destabilizing | 0.953 | D | 0.731 | prob.delet. | 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.