Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2744 | 8455;8456;8457 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| N2AB | 2744 | 8455;8456;8457 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| N2A | 2744 | 8455;8456;8457 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| N2B | 2698 | 8317;8318;8319 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| Novex-1 | 2698 | 8317;8318;8319 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| Novex-2 | 2698 | 8317;8318;8319 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
| Novex-3 | 2744 | 8455;8456;8457 | chr2:178770562;178770561;178770560 | chr2:179635289;179635288;179635287 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | rs556908341  |
-0.369 | 1.0 | D | 0.575 | 0.653 | 0.747641037427 | gnomAD-2.1.1 | 2.66747E-04 | None | None | None | None | I | None | 0 | 2.89E-05 | None | 0 | 0 | None | 2.15588E-03 | None | 0 | 0 | 0 |
| G/A | rs556908341 |
-0.369 | 1.0 | D | 0.575 | 0.653 | 0.747641037427 | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.48653E-03 | 0 |
| G/A | rs556908341 |
-0.369 | 1.0 | D | 0.575 | 0.653 | 0.747641037427 | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| G/A | rs556908341 |
-0.369 | 1.0 | D | 0.575 | 0.653 | 0.747641037427 | gnomAD-4.0.0 | 1.19569E-04 | None | None | None | None | I | None | 1.33259E-05 | 1.66617E-05 | None | 0 | 0 | None | 0 | 1.64962E-04 | 0 | 2.00922E-03 | 1.11989E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.3261 | likely_benign | 0.4856 | ambiguous | -0.326 | Destabilizing | 1.0 | D | 0.575 | neutral | D | 0.711514938 | None | None | I |
| G/C | 0.6347 | likely_pathogenic | 0.779 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| G/D | 0.3997 | ambiguous | 0.5341 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| G/E | 0.5655 | likely_pathogenic | 0.7199 | pathogenic | -0.825 | Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.626724893 | None | None | I |
| G/F | 0.9232 | likely_pathogenic | 0.97 | pathogenic | -1.008 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| G/H | 0.7095 | likely_pathogenic | 0.8287 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| G/I | 0.8316 | likely_pathogenic | 0.9324 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| G/K | 0.7764 | likely_pathogenic | 0.8653 | pathogenic | -0.891 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| G/L | 0.8523 | likely_pathogenic | 0.9282 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| G/M | 0.8294 | likely_pathogenic | 0.9216 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| G/N | 0.3487 | ambiguous | 0.4673 | ambiguous | -0.626 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| G/P | 0.9893 | likely_pathogenic | 0.9966 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | I |
| G/Q | 0.6163 | likely_pathogenic | 0.7369 | pathogenic | -0.884 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| G/R | 0.6172 | likely_pathogenic | 0.7481 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | D | 0.711514938 | None | None | I |
| G/S | 0.1535 | likely_benign | 0.2193 | benign | -0.758 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| G/T | 0.4672 | ambiguous | 0.6652 | pathogenic | -0.843 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| G/V | 0.7418 | likely_pathogenic | 0.8843 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.662 | neutral | D | 0.710095528 | None | None | I |
| G/W | 0.8341 | likely_pathogenic | 0.9274 | pathogenic | -1.136 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| G/Y | 0.8231 | likely_pathogenic | 0.9261 | pathogenic | -0.825 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | 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.