Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25074 | 75445;75446;75447 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| N2AB | 23433 | 70522;70523;70524 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| N2A | 22506 | 67741;67742;67743 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| N2B | 16009 | 48250;48251;48252 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| Novex-1 | 16134 | 48625;48626;48627 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| Novex-2 | 16201 | 48826;48827;48828 | chr2:178570912;178570911;178570910 | chr2:179435639;179435638;179435637 |
| 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/H | rs780776048  |
-0.396 | 0.627 | N | 0.413 | 0.196 | 0.211220785272 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/H | rs780776048 |
-0.396 | 0.627 | N | 0.413 | 0.196 | 0.211220785272 | gnomAD-4.0.0 | 3.18337E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86549E-05 | 0 |
| D/N | rs780776048 |
-0.103 | 0.001 | N | 0.185 | 0.116 | 0.128392430309 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/N | rs780776048 |
-0.103 | 0.001 | N | 0.185 | 0.116 | 0.128392430309 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85935E-06 | 0 | 0 |
| D/Y | None | None | 0.912 | N | 0.557 | 0.303 | 0.568036332872 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85935E-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 | 0.2829 | likely_benign | 0.3464 | ambiguous | -0.419 | Destabilizing | 0.193 | N | 0.491 | neutral | N | 0.453238032 | None | None | N |
| D/C | 0.7321 | likely_pathogenic | 0.778 | pathogenic | -0.17 | Destabilizing | 0.981 | D | 0.599 | neutral | None | None | None | None | N |
| D/E | 0.2535 | likely_benign | 0.2825 | benign | -0.456 | Destabilizing | 0.003 | N | 0.191 | neutral | N | 0.452968673 | None | None | N |
| D/F | 0.6838 | likely_pathogenic | 0.7406 | pathogenic | -0.356 | Destabilizing | 0.932 | D | 0.555 | neutral | None | None | None | None | N |
| D/G | 0.1216 | likely_benign | 0.135 | benign | -0.662 | Destabilizing | 0.001 | N | 0.269 | neutral | N | 0.367112196 | None | None | N |
| D/H | 0.4046 | ambiguous | 0.4824 | ambiguous | -0.489 | Destabilizing | 0.627 | D | 0.413 | neutral | N | 0.494007219 | None | None | N |
| D/I | 0.6616 | likely_pathogenic | 0.735 | pathogenic | 0.188 | Stabilizing | 0.818 | D | 0.562 | neutral | None | None | None | None | N |
| D/K | 0.5659 | likely_pathogenic | 0.64 | pathogenic | -0.358 | Destabilizing | 0.241 | N | 0.379 | neutral | None | None | None | None | N |
| D/L | 0.5475 | ambiguous | 0.6253 | pathogenic | 0.188 | Stabilizing | 0.69 | D | 0.555 | neutral | None | None | None | None | N |
| D/M | 0.7249 | likely_pathogenic | 0.7925 | pathogenic | 0.419 | Stabilizing | 0.981 | D | 0.548 | neutral | None | None | None | None | N |
| D/N | 0.0722 | likely_benign | 0.1084 | benign | -0.433 | Destabilizing | 0.001 | N | 0.185 | neutral | N | 0.404502722 | None | None | N |
| D/P | 0.9211 | likely_pathogenic | 0.9393 | pathogenic | 0.008 | Stabilizing | 0.818 | D | 0.432 | neutral | None | None | None | None | N |
| D/Q | 0.4933 | ambiguous | 0.5711 | pathogenic | -0.379 | Destabilizing | 0.69 | D | 0.389 | neutral | None | None | None | None | N |
| D/R | 0.6147 | likely_pathogenic | 0.6634 | pathogenic | -0.156 | Destabilizing | 0.69 | D | 0.542 | neutral | None | None | None | None | N |
| D/S | 0.1548 | likely_benign | 0.2069 | benign | -0.638 | Destabilizing | 0.116 | N | 0.31 | neutral | None | None | None | None | N |
| D/T | 0.3998 | ambiguous | 0.5045 | ambiguous | -0.466 | Destabilizing | 0.388 | N | 0.384 | neutral | None | None | None | None | N |
| D/V | 0.4831 | ambiguous | 0.5504 | ambiguous | 0.008 | Stabilizing | 0.773 | D | 0.555 | neutral | N | 0.483752275 | None | None | N |
| D/W | 0.9058 | likely_pathogenic | 0.9185 | pathogenic | -0.274 | Destabilizing | 0.981 | D | 0.65 | neutral | None | None | None | None | N |
| D/Y | 0.2921 | likely_benign | 0.3205 | benign | -0.171 | Destabilizing | 0.912 | D | 0.557 | neutral | N | 0.477923045 | 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.