Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3099 | 9520;9521;9522 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| N2AB | 3099 | 9520;9521;9522 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| N2A | 3099 | 9520;9521;9522 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| N2B | 3053 | 9382;9383;9384 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| Novex-1 | 3053 | 9382;9383;9384 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| Novex-2 | 3053 | 9382;9383;9384 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
| Novex-3 | 3099 | 9520;9521;9522 | chr2:178768024;178768023;178768022 | chr2:179632751;179632750;179632749 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs747584198  |
-0.174 | 0.029 | N | 0.391 | 0.114 | 0.53586618445 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| I/N | rs747584198 |
-0.174 | 0.029 | N | 0.391 | 0.114 | 0.53586618445 | gnomAD-4.0.0 | 1.59055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85651E-06 | 0 | 0 |
| I/V | rs2090820350 |
None | None | N | 0.102 | 0.061 | 0.173771789658 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2090820350 |
None | None | N | 0.102 | 0.061 | 0.173771789658 | gnomAD-4.0.0 | 6.56927E-06 | None | None | None | None | N | None | 0 | 6.54365E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.319 | likely_benign | 0.2149 | benign | -0.76 | Destabilizing | None | N | 0.094 | neutral | None | None | None | None | N |
| I/C | 0.6338 | likely_pathogenic | 0.5556 | ambiguous | -0.891 | Destabilizing | 0.356 | N | 0.288 | neutral | None | None | None | None | N |
| I/D | 0.5855 | likely_pathogenic | 0.4212 | ambiguous | -0.166 | Destabilizing | 0.038 | N | 0.405 | neutral | None | None | None | None | N |
| I/E | 0.4929 | ambiguous | 0.3516 | ambiguous | -0.211 | Destabilizing | 0.038 | N | 0.382 | neutral | None | None | None | None | N |
| I/F | 0.1336 | likely_benign | 0.1146 | benign | -0.581 | Destabilizing | 0.029 | N | 0.256 | neutral | N | 0.465105968 | None | None | N |
| I/G | 0.5549 | ambiguous | 0.3956 | ambiguous | -0.962 | Destabilizing | 0.016 | N | 0.33 | neutral | None | None | None | None | N |
| I/H | 0.4819 | ambiguous | 0.3626 | ambiguous | -0.161 | Destabilizing | 0.356 | N | 0.281 | neutral | None | None | None | None | N |
| I/K | 0.4186 | ambiguous | 0.297 | benign | -0.53 | Destabilizing | 0.038 | N | 0.393 | neutral | None | None | None | None | N |
| I/L | 0.0796 | likely_benign | 0.0651 | benign | -0.323 | Destabilizing | None | N | 0.093 | neutral | N | 0.397125976 | None | None | N |
| I/M | 0.0763 | likely_benign | 0.0689 | benign | -0.575 | Destabilizing | 0.093 | N | 0.277 | neutral | N | 0.475119296 | None | None | N |
| I/N | 0.2264 | likely_benign | 0.1453 | benign | -0.459 | Destabilizing | 0.029 | N | 0.391 | neutral | N | 0.452192385 | None | None | N |
| I/P | 0.4146 | ambiguous | 0.2851 | benign | -0.437 | Destabilizing | 0.072 | N | 0.409 | neutral | None | None | None | None | N |
| I/Q | 0.4043 | ambiguous | 0.2839 | benign | -0.584 | Destabilizing | 0.214 | N | 0.365 | neutral | None | None | None | None | N |
| I/R | 0.3492 | ambiguous | 0.246 | benign | -0.046 | Destabilizing | 0.214 | N | 0.393 | neutral | None | None | None | None | N |
| I/S | 0.3066 | likely_benign | 0.196 | benign | -0.956 | Destabilizing | None | N | 0.153 | neutral | N | 0.396556322 | None | None | N |
| I/T | 0.2834 | likely_benign | 0.1747 | benign | -0.88 | Destabilizing | 0.012 | N | 0.292 | neutral | N | 0.452647606 | None | None | N |
| I/V | 0.0784 | likely_benign | 0.0714 | benign | -0.437 | Destabilizing | None | N | 0.102 | neutral | N | 0.445828324 | None | None | N |
| I/W | 0.6318 | likely_pathogenic | 0.5806 | pathogenic | -0.613 | Destabilizing | 0.864 | D | 0.275 | neutral | None | None | None | None | N |
| I/Y | 0.4269 | ambiguous | 0.3581 | ambiguous | -0.379 | Destabilizing | 0.356 | N | 0.37 | 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.