Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2303 | 7132;7133;7134 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| N2AB | 2303 | 7132;7133;7134 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| N2A | 2303 | 7132;7133;7134 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| N2B | 2257 | 6994;6995;6996 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| Novex-1 | 2257 | 6994;6995;6996 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| Novex-2 | 2257 | 6994;6995;6996 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
| Novex-3 | 2303 | 7132;7133;7134 | chr2:178774357;178774356;178774355 | chr2:179639084;179639083;179639082 |
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/E | None | None | 0.002 | N | 0.175 | 0.072 | 0.0551355673512 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| D/G | None | None | None | N | 0.212 | 0.104 | 0.0138822411134 | gnomAD-4.0.0 | 1.59064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85687E-06 | 0 | 0 |
| D/H | rs779125886  |
0.3 | 0.484 | N | 0.357 | 0.108 | 0.0551355673512 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| D/H | rs779125886 |
0.3 | 0.484 | N | 0.357 | 0.108 | 0.0551355673512 | gnomAD-4.0.0 | 1.4366E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.8886E-05 | 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 | 0.1193 | likely_benign | 0.1219 | benign | -0.236 | Destabilizing | 0.062 | N | 0.361 | neutral | N | 0.448102578 | None | None | N |
| D/C | 0.3939 | ambiguous | 0.4107 | ambiguous | -0.166 | Destabilizing | 0.935 | D | 0.474 | neutral | None | None | None | None | N |
| D/E | 0.1192 | likely_benign | 0.1235 | benign | -0.257 | Destabilizing | 0.002 | N | 0.175 | neutral | N | 0.445370032 | None | None | N |
| D/F | 0.4878 | ambiguous | 0.4989 | ambiguous | -0.088 | Destabilizing | 0.791 | D | 0.433 | neutral | None | None | None | None | N |
| D/G | 0.0577 | likely_benign | 0.0596 | benign | -0.415 | Destabilizing | None | N | 0.212 | neutral | N | 0.318724546 | None | None | N |
| D/H | 0.1751 | likely_benign | 0.1799 | benign | 0.303 | Stabilizing | 0.484 | N | 0.357 | neutral | N | 0.456864222 | None | None | N |
| D/I | 0.3196 | likely_benign | 0.3253 | benign | 0.183 | Stabilizing | 0.555 | D | 0.435 | neutral | None | None | None | None | N |
| D/K | 0.1936 | likely_benign | 0.198 | benign | 0.315 | Stabilizing | 0.149 | N | 0.327 | neutral | None | None | None | None | N |
| D/L | 0.3175 | likely_benign | 0.3176 | benign | 0.183 | Stabilizing | 0.38 | N | 0.437 | neutral | None | None | None | None | N |
| D/M | 0.4526 | ambiguous | 0.4653 | ambiguous | 0.129 | Stabilizing | 0.935 | D | 0.425 | neutral | None | None | None | None | N |
| D/N | 0.0677 | likely_benign | 0.0673 | benign | -0.071 | Destabilizing | 0.002 | N | 0.26 | neutral | N | 0.434332785 | None | None | N |
| D/P | 0.7504 | likely_pathogenic | 0.7446 | pathogenic | 0.064 | Stabilizing | 0.555 | D | 0.377 | neutral | None | None | None | None | N |
| D/Q | 0.195 | likely_benign | 0.202 | benign | -0.024 | Destabilizing | 0.38 | N | 0.343 | neutral | None | None | None | None | N |
| D/R | 0.2179 | likely_benign | 0.2289 | benign | 0.577 | Stabilizing | 0.38 | N | 0.405 | neutral | None | None | None | None | N |
| D/S | 0.0829 | likely_benign | 0.084 | benign | -0.162 | Destabilizing | 0.081 | N | 0.322 | neutral | None | None | None | None | N |
| D/T | 0.169 | likely_benign | 0.1713 | benign | -0.013 | Destabilizing | 0.149 | N | 0.359 | neutral | None | None | None | None | N |
| D/V | 0.2205 | likely_benign | 0.2247 | benign | 0.064 | Stabilizing | 0.484 | N | 0.437 | neutral | N | 0.451312941 | None | None | N |
| D/W | 0.7685 | likely_pathogenic | 0.794 | pathogenic | 0.061 | Stabilizing | 0.935 | D | 0.547 | neutral | None | None | None | None | N |
| D/Y | 0.1998 | likely_benign | 0.2053 | benign | 0.155 | Stabilizing | 0.741 | D | 0.431 | neutral | N | 0.450174381 | 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.