Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27397 | 82414;82415;82416 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| N2AB | 25756 | 77491;77492;77493 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| N2A | 24829 | 74710;74711;74712 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| N2B | 18332 | 55219;55220;55221 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| Novex-1 | 18457 | 55594;55595;55596 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| Novex-2 | 18524 | 55795;55796;55797 | chr2:178563943;178563942;178563941 | chr2:179428670;179428669;179428668 |
| 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 | 1.0 | N | 0.713 | 0.562 | 0.536051623013 | gnomAD-4.0.0 | 6.84238E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9951E-07 | 0 | 0 |
| D/V | rs1230727377  |
0.162 | 1.0 | N | 0.696 | 0.534 | 0.678876107029 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/V | rs1230727377 |
0.162 | 1.0 | N | 0.696 | 0.534 | 0.678876107029 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79902E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7295 | likely_pathogenic | 0.6998 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.498324584 | None | None | I |
| D/C | 0.9491 | likely_pathogenic | 0.9375 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| D/E | 0.6894 | likely_pathogenic | 0.6786 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.439 | neutral | N | 0.490398092 | None | None | I |
| D/F | 0.9597 | likely_pathogenic | 0.9542 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/G | 0.6679 | likely_pathogenic | 0.6264 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.510378906 | None | None | I |
| D/H | 0.8487 | likely_pathogenic | 0.8234 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.511428863 | None | None | I |
| D/I | 0.8903 | likely_pathogenic | 0.8803 | pathogenic | 0.437 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/K | 0.917 | likely_pathogenic | 0.9036 | pathogenic | -0.037 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/L | 0.9089 | likely_pathogenic | 0.8891 | pathogenic | 0.437 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| D/M | 0.951 | likely_pathogenic | 0.9452 | pathogenic | 0.844 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| D/N | 0.2337 | likely_benign | 0.2212 | benign | -0.293 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.518193587 | None | None | I |
| D/P | 0.9655 | likely_pathogenic | 0.9586 | pathogenic | 0.233 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/Q | 0.8948 | likely_pathogenic | 0.8806 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| D/R | 0.9235 | likely_pathogenic | 0.9097 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/S | 0.5016 | ambiguous | 0.4699 | ambiguous | -0.45 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/T | 0.6721 | likely_pathogenic | 0.6563 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/V | 0.7632 | likely_pathogenic | 0.7439 | pathogenic | 0.233 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.518657338 | None | None | I |
| D/W | 0.9913 | likely_pathogenic | 0.9891 | pathogenic | -0.344 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/Y | 0.7336 | likely_pathogenic | 0.684 | pathogenic | -0.158 | Destabilizing | 1.0 | D | 0.631 | neutral | D | 0.546422832 | 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.