Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3035 | 9328;9329;9330 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| N2AB | 3035 | 9328;9329;9330 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| N2A | 3035 | 9328;9329;9330 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| N2B | 2989 | 9190;9191;9192 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| Novex-1 | 2989 | 9190;9191;9192 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| Novex-2 | 2989 | 9190;9191;9192 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
| Novex-3 | 3035 | 9328;9329;9330 | chr2:178768733;178768732;178768731 | chr2:179633460;179633459;179633458 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.031 | N | 0.197 | 0.253 | 0.267755039894 | gnomAD-4.0.0 | 6.84092E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 0 | 0 |
| A/T | rs745745046  |
-0.94 | 0.961 | N | 0.512 | 0.309 | 0.398872588132 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs745745046 |
-0.94 | 0.961 | N | 0.512 | 0.309 | 0.398872588132 | gnomAD-4.0.0 | 1.59061E-06 | None | None | None | None | N | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | None | None | 0.248 | N | 0.359 | 0.288 | 0.415055319159 | gnomAD-4.0.0 | 2.05228E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69789E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8596 | likely_pathogenic | 0.8639 | pathogenic | -0.89 | Destabilizing | 1.0 | D | 0.545 | neutral | None | None | None | None | N |
| A/D | 0.9429 | likely_pathogenic | 0.9138 | pathogenic | -1.031 | Destabilizing | 0.994 | D | 0.669 | neutral | N | 0.513429629 | None | None | N |
| A/E | 0.8275 | likely_pathogenic | 0.7462 | pathogenic | -1.056 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| A/F | 0.8956 | likely_pathogenic | 0.8685 | pathogenic | -1.0 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/G | 0.4463 | ambiguous | 0.3805 | ambiguous | -1.152 | Destabilizing | 0.031 | N | 0.197 | neutral | N | 0.512558387 | None | None | N |
| A/H | 0.9445 | likely_pathogenic | 0.9319 | pathogenic | -1.305 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/I | 0.8439 | likely_pathogenic | 0.7745 | pathogenic | -0.326 | Destabilizing | 0.942 | D | 0.591 | neutral | None | None | None | None | N |
| A/K | 0.9476 | likely_pathogenic | 0.9204 | pathogenic | -1.155 | Destabilizing | 0.996 | D | 0.637 | neutral | None | None | None | None | N |
| A/L | 0.7646 | likely_pathogenic | 0.7118 | pathogenic | -0.326 | Destabilizing | 0.942 | D | 0.595 | neutral | None | None | None | None | N |
| A/M | 0.7257 | likely_pathogenic | 0.6462 | pathogenic | -0.262 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| A/N | 0.8502 | likely_pathogenic | 0.8051 | pathogenic | -0.911 | Destabilizing | 0.996 | D | 0.722 | prob.delet. | None | None | None | None | N |
| A/P | 0.9846 | likely_pathogenic | 0.9722 | pathogenic | -0.472 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | D | 0.595027038 | None | None | N |
| A/Q | 0.8081 | likely_pathogenic | 0.7627 | pathogenic | -1.048 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| A/R | 0.8781 | likely_pathogenic | 0.8437 | pathogenic | -0.829 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/S | 0.2331 | likely_benign | 0.1799 | benign | -1.292 | Destabilizing | 0.961 | D | 0.549 | neutral | N | 0.453017927 | None | None | N |
| A/T | 0.4484 | ambiguous | 0.316 | benign | -1.217 | Destabilizing | 0.961 | D | 0.512 | neutral | N | 0.512988263 | None | None | N |
| A/V | 0.5968 | likely_pathogenic | 0.4816 | ambiguous | -0.472 | Destabilizing | 0.248 | N | 0.359 | neutral | N | 0.505212078 | None | None | N |
| A/W | 0.9896 | likely_pathogenic | 0.9868 | pathogenic | -1.355 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| A/Y | 0.9447 | likely_pathogenic | 0.9359 | pathogenic | -0.937 | Destabilizing | 0.999 | D | 0.735 | 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.