Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32307 | 97144;97145;97146 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| N2AB | 30666 | 92221;92222;92223 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| N2A | 29739 | 89440;89441;89442 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| N2B | 23242 | 69949;69950;69951 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| Novex-1 | 23367 | 70324;70325;70326 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| Novex-2 | 23434 | 70525;70526;70527 | chr2:178542935;178542934;178542933 | chr2:179407662;179407661;179407660 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 0.201 | D | 0.581 | 0.279 | 0.451786746415 | gnomAD-4.0.0 | 2.06866E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.60456E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs942897847  |
-0.007 | 0.334 | D | 0.625 | 0.268 | 0.287603790349 | gnomAD-2.1.1 | 1.82E-05 | None | None | None | None | I | None | 2.07452E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs942897847 |
-0.007 | 0.334 | D | 0.625 | 0.268 | 0.287603790349 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 1.20604E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs942897847 |
-0.007 | 0.334 | D | 0.625 | 0.268 | 0.287603790349 | gnomAD-4.0.0 | 6.24064E-06 | None | None | None | None | I | None | 1.20556E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.61415E-05 |
| D/N | rs1474585549 |
0.345 | 0.081 | D | 0.326 | 0.242 | 0.27855597813 | gnomAD-2.1.1 | 1.24E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.48E-05 | None | 0 | 1.82E-05 | 0 |
| D/N | rs1474585549 |
0.345 | 0.081 | D | 0.326 | 0.242 | 0.27855597813 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1474585549 |
0.345 | 0.081 | D | 0.326 | 0.242 | 0.27855597813 | gnomAD-4.0.0 | 1.12479E-05 | None | None | None | None | I | None | 0 | 1.69394E-05 | None | 0 | 2.24185E-05 | None | 0 | 0 | 5.97895E-06 | 7.81424E-05 | 3.23394E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4096 | ambiguous | 0.4132 | ambiguous | -0.149 | Destabilizing | 0.201 | N | 0.581 | neutral | D | 0.530883244 | None | None | I |
| D/C | 0.8216 | likely_pathogenic | 0.8015 | pathogenic | -0.017 | Destabilizing | 0.982 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/E | 0.4297 | ambiguous | 0.4183 | ambiguous | -0.279 | Destabilizing | 0.002 | N | 0.32 | neutral | N | 0.510217183 | None | None | I |
| D/F | 0.8299 | likely_pathogenic | 0.8284 | pathogenic | -0.055 | Destabilizing | 0.982 | D | 0.693 | prob.neutral | None | None | None | None | I |
| D/G | 0.6272 | likely_pathogenic | 0.6516 | pathogenic | -0.335 | Destabilizing | 0.334 | N | 0.625 | neutral | D | 0.531576677 | None | None | I |
| D/H | 0.5052 | ambiguous | 0.4707 | ambiguous | 0.231 | Stabilizing | 0.972 | D | 0.664 | neutral | D | 0.531576677 | None | None | I |
| D/I | 0.5404 | ambiguous | 0.5414 | ambiguous | 0.291 | Stabilizing | 0.826 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/K | 0.7524 | likely_pathogenic | 0.748 | pathogenic | 0.418 | Stabilizing | 0.25 | N | 0.643 | neutral | None | None | None | None | I |
| D/L | 0.6422 | likely_pathogenic | 0.6407 | pathogenic | 0.291 | Stabilizing | 0.7 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/M | 0.8187 | likely_pathogenic | 0.8159 | pathogenic | 0.272 | Stabilizing | 0.982 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/N | 0.1594 | likely_benign | 0.142 | benign | 0.021 | Stabilizing | 0.081 | N | 0.326 | neutral | D | 0.530709885 | None | None | I |
| D/P | 0.9021 | likely_pathogenic | 0.9171 | pathogenic | 0.166 | Stabilizing | 0.826 | D | 0.675 | neutral | None | None | None | None | I |
| D/Q | 0.6175 | likely_pathogenic | 0.605 | pathogenic | 0.078 | Stabilizing | 0.539 | D | 0.657 | neutral | None | None | None | None | I |
| D/R | 0.7281 | likely_pathogenic | 0.7294 | pathogenic | 0.602 | Stabilizing | 0.539 | D | 0.665 | neutral | None | None | None | None | I |
| D/S | 0.2857 | likely_benign | 0.2563 | benign | -0.041 | Destabilizing | 0.25 | N | 0.601 | neutral | None | None | None | None | I |
| D/T | 0.5418 | ambiguous | 0.5248 | ambiguous | 0.113 | Stabilizing | 0.7 | D | 0.657 | neutral | None | None | None | None | I |
| D/V | 0.3805 | ambiguous | 0.38 | ambiguous | 0.166 | Stabilizing | 0.638 | D | 0.7 | prob.neutral | D | 0.531750035 | None | None | I |
| D/W | 0.9585 | likely_pathogenic | 0.9633 | pathogenic | 0.062 | Stabilizing | 0.982 | D | 0.73 | prob.delet. | None | None | None | None | I |
| D/Y | 0.4015 | ambiguous | 0.4103 | ambiguous | 0.182 | Stabilizing | 0.99 | D | 0.691 | prob.neutral | D | 0.532096752 | 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.