Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1766 | 5521;5522;5523 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| N2AB | 1766 | 5521;5522;5523 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| N2A | 1766 | 5521;5522;5523 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| N2B | 1720 | 5383;5384;5385 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| Novex-1 | 1720 | 5383;5384;5385 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| Novex-2 | 1720 | 5383;5384;5385 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
| Novex-3 | 1766 | 5521;5522;5523 | chr2:178776568;178776567;178776566 | chr2:179641295;179641294;179641293 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | None | None | 0.836 | N | 0.481 | 0.35 | 0.846797359206 | gnomAD-4.0.0 | 6.84445E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99303E-07 | 0 | 0 |
| V/I | rs149494502  |
-0.204 | 0.021 | N | 0.326 | 0.131 | None | gnomAD-2.1.1 | 4.97E-05 | None | None | None | None | N | None | 2.40385E-04 | 0 | None | 0 | 1.00523E-04 | None | 6.53E-05 | None | 0 | 3.11E-05 | 0 |
| V/I | rs149494502 |
-0.204 | 0.021 | N | 0.326 | 0.131 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.69049E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs149494502 |
-0.204 | 0.021 | N | 0.326 | 0.131 | None | gnomAD-4.0.0 | 3.53344E-05 | None | None | None | None | N | None | 2.40378E-04 | 0 | None | 3.37769E-05 | 1.11443E-04 | None | 0 | 0 | 2.6271E-05 | 2.19597E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1322 | likely_benign | 0.1071 | benign | -1.358 | Destabilizing | None | N | 0.221 | neutral | N | 0.431389093 | None | None | N |
| V/C | 0.8479 | likely_pathogenic | 0.7915 | pathogenic | -0.778 | Destabilizing | 0.909 | D | 0.474 | neutral | None | None | None | None | N |
| V/D | 0.6785 | likely_pathogenic | 0.6321 | pathogenic | -1.083 | Destabilizing | 0.497 | N | 0.565 | neutral | N | 0.421956036 | None | None | N |
| V/E | 0.5617 | ambiguous | 0.5399 | ambiguous | -0.987 | Destabilizing | 0.567 | D | 0.5 | neutral | None | None | None | None | N |
| V/F | 0.3397 | likely_benign | 0.3336 | benign | -0.805 | Destabilizing | 0.836 | D | 0.481 | neutral | N | 0.510477083 | None | None | N |
| V/G | 0.3168 | likely_benign | 0.2783 | benign | -1.766 | Destabilizing | 0.124 | N | 0.493 | neutral | N | 0.414659015 | None | None | N |
| V/H | 0.7863 | likely_pathogenic | 0.7666 | pathogenic | -1.275 | Destabilizing | 0.968 | D | 0.571 | neutral | None | None | None | None | N |
| V/I | 0.1084 | likely_benign | 0.1051 | benign | -0.303 | Destabilizing | 0.021 | N | 0.326 | neutral | N | 0.510617331 | None | None | N |
| V/K | 0.6983 | likely_pathogenic | 0.6843 | pathogenic | -0.992 | Destabilizing | 0.567 | D | 0.501 | neutral | None | None | None | None | N |
| V/L | 0.3432 | ambiguous | 0.2892 | benign | -0.303 | Destabilizing | 0.129 | N | 0.463 | neutral | N | 0.505723341 | None | None | N |
| V/M | 0.2375 | likely_benign | 0.2123 | benign | -0.24 | Destabilizing | 0.726 | D | 0.481 | neutral | None | None | None | None | N |
| V/N | 0.4118 | ambiguous | 0.3845 | ambiguous | -0.987 | Destabilizing | 0.726 | D | 0.584 | neutral | None | None | None | None | N |
| V/P | 0.5333 | ambiguous | 0.4141 | ambiguous | -0.621 | Destabilizing | 0.567 | D | 0.519 | neutral | None | None | None | None | N |
| V/Q | 0.5562 | ambiguous | 0.5448 | ambiguous | -1.003 | Destabilizing | 0.726 | D | 0.543 | neutral | None | None | None | None | N |
| V/R | 0.6562 | likely_pathogenic | 0.6488 | pathogenic | -0.655 | Destabilizing | 0.567 | D | 0.586 | neutral | None | None | None | None | N |
| V/S | 0.225 | likely_benign | 0.1959 | benign | -1.612 | Destabilizing | 0.157 | N | 0.437 | neutral | None | None | None | None | N |
| V/T | 0.1969 | likely_benign | 0.167 | benign | -1.389 | Destabilizing | 0.157 | N | 0.508 | neutral | None | None | None | None | N |
| V/W | 0.9453 | likely_pathogenic | 0.9371 | pathogenic | -1.13 | Destabilizing | 0.968 | D | 0.561 | neutral | None | None | None | None | N |
| V/Y | 0.7842 | likely_pathogenic | 0.7724 | pathogenic | -0.747 | Destabilizing | 0.726 | D | 0.488 | neutral | 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.