Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25237 | 75934;75935;75936 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| N2AB | 23596 | 71011;71012;71013 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| N2A | 22669 | 68230;68231;68232 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| N2B | 16172 | 48739;48740;48741 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| Novex-1 | 16297 | 49114;49115;49116 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| Novex-2 | 16364 | 49315;49316;49317 | chr2:178570423;178570422;178570421 | chr2:179435150;179435149;179435148 |
| 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/N | rs756017651  |
-1.995 | 0.998 | D | 0.849 | 0.562 | 0.845632121002 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 4.65E-05 | 8.96E-06 | 0 |
| I/N | rs756017651 |
-1.995 | 0.998 | D | 0.849 | 0.562 | 0.845632121002 | gnomAD-4.0.0 | 6.37048E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.88686E-05 | 0 | 0 | 2.86582E-05 | 3.02718E-05 |
| I/T | rs756017651 |
-2.42 | 0.961 | D | 0.726 | 0.5 | 0.725541513621 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs756017651 |
-2.42 | 0.961 | D | 0.726 | 0.5 | 0.725541513621 | gnomAD-4.0.0 | 1.59262E-06 | None | None | None | None | I | None | 5.66251E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1412324143 |
-1.67 | 0.122 | N | 0.211 | 0.071 | 0.563099480232 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| I/V | rs1412324143 |
-1.67 | 0.122 | N | 0.211 | 0.071 | 0.563099480232 | gnomAD-4.0.0 | 1.36891E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87688E-05 | 0 | 8.99607E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9376 | likely_pathogenic | 0.9541 | pathogenic | -2.358 | Highly Destabilizing | 0.931 | D | 0.673 | neutral | None | None | None | None | I |
| I/C | 0.9356 | likely_pathogenic | 0.9568 | pathogenic | -1.408 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| I/D | 0.995 | likely_pathogenic | 0.9964 | pathogenic | -2.504 | Highly Destabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | I |
| I/E | 0.9898 | likely_pathogenic | 0.9924 | pathogenic | -2.411 | Highly Destabilizing | 0.999 | D | 0.844 | deleterious | None | None | None | None | I |
| I/F | 0.8638 | likely_pathogenic | 0.8907 | pathogenic | -1.62 | Destabilizing | 0.994 | D | 0.685 | prob.neutral | D | 0.540501484 | None | None | I |
| I/G | 0.9881 | likely_pathogenic | 0.9917 | pathogenic | -2.787 | Highly Destabilizing | 0.999 | D | 0.854 | deleterious | None | None | None | None | I |
| I/H | 0.9885 | likely_pathogenic | 0.9921 | pathogenic | -2.18 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| I/K | 0.972 | likely_pathogenic | 0.9795 | pathogenic | -1.823 | Destabilizing | 0.999 | D | 0.842 | deleterious | None | None | None | None | I |
| I/L | 0.3451 | ambiguous | 0.4179 | ambiguous | -1.177 | Destabilizing | 0.689 | D | 0.407 | neutral | N | 0.490290096 | None | None | I |
| I/M | 0.4592 | ambiguous | 0.5195 | ambiguous | -0.812 | Destabilizing | 0.994 | D | 0.679 | prob.neutral | D | 0.554392685 | None | None | I |
| I/N | 0.924 | likely_pathogenic | 0.9402 | pathogenic | -1.807 | Destabilizing | 0.998 | D | 0.849 | deleterious | D | 0.525946082 | None | None | I |
| I/P | 0.9651 | likely_pathogenic | 0.9762 | pathogenic | -1.546 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | I |
| I/Q | 0.9853 | likely_pathogenic | 0.989 | pathogenic | -1.89 | Destabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | I |
| I/R | 0.9606 | likely_pathogenic | 0.9716 | pathogenic | -1.251 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | I |
| I/S | 0.9473 | likely_pathogenic | 0.9557 | pathogenic | -2.404 | Highly Destabilizing | 0.994 | D | 0.836 | deleterious | D | 0.531768979 | None | None | I |
| I/T | 0.8549 | likely_pathogenic | 0.8843 | pathogenic | -2.192 | Highly Destabilizing | 0.961 | D | 0.726 | prob.delet. | D | 0.525185614 | None | None | I |
| I/V | 0.0919 | likely_benign | 0.1 | benign | -1.546 | Destabilizing | 0.122 | N | 0.211 | neutral | N | 0.482929007 | None | None | I |
| I/W | 0.9962 | likely_pathogenic | 0.9975 | pathogenic | -1.914 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| I/Y | 0.9762 | likely_pathogenic | 0.9829 | pathogenic | -1.676 | Destabilizing | 0.999 | D | 0.782 | 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.