Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16000 | 48223;48224;48225 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| N2AB | 14359 | 43300;43301;43302 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| N2A | 13432 | 40519;40520;40521 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| N2B | 6935 | 21028;21029;21030 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| Novex-1 | 7060 | 21403;21404;21405 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| Novex-2 | 7127 | 21604;21605;21606 | chr2:178616891;178616890;178616889 | chr2:179481618;179481617;179481616 |
| 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 | rs201388509  |
0.361 | 0.667 | N | 0.421 | 0.318 | None | gnomAD-2.1.1 | 8.75393E-04 | None | None | None | None | N | None | 1.24121E-04 | 3.97118E-04 | None | 0 | 0 | None | 0 | None | 1.87895E-03 | 1.34673E-03 | 1.26796E-03 |
| D/H | rs201388509 |
0.361 | 0.667 | N | 0.421 | 0.318 | None | gnomAD-3.1.2 | 4.74002E-04 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 1.22411E-03 | 0 | 8.24451E-04 | 0 | 0 |
| D/H | rs201388509 |
0.361 | 0.667 | N | 0.421 | 0.318 | None | gnomAD-4.0.0 | 6.67874E-04 | None | None | None | None | N | None | 9.35829E-05 | 2.50509E-04 | None | 3.38364E-05 | 0 | None | 1.76546E-03 | 0 | 7.53889E-04 | 0 | 8.33467E-04 |
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 | 0.2119 | likely_benign | 0.2228 | benign | 0.068 | Stabilizing | 0.124 | N | 0.418 | neutral | N | 0.435562118 | None | None | N |
| D/C | 0.6087 | likely_pathogenic | 0.6208 | pathogenic | -0.197 | Destabilizing | 0.968 | D | 0.585 | neutral | None | None | None | None | N |
| D/E | 0.1322 | likely_benign | 0.14 | benign | -0.452 | Destabilizing | None | N | 0.166 | neutral | N | 0.445775766 | None | None | N |
| D/F | 0.716 | likely_pathogenic | 0.7016 | pathogenic | -0.131 | Destabilizing | 0.89 | D | 0.499 | neutral | None | None | None | None | N |
| D/G | 0.1106 | likely_benign | 0.113 | benign | 0.004 | Stabilizing | 0.001 | N | 0.263 | neutral | N | 0.423154768 | None | None | N |
| D/H | 0.2929 | likely_benign | 0.3029 | benign | 0.51 | Stabilizing | 0.667 | D | 0.421 | neutral | N | 0.504754178 | None | None | N |
| D/I | 0.5013 | ambiguous | 0.5101 | ambiguous | 0.165 | Stabilizing | 0.726 | D | 0.489 | neutral | None | None | None | None | N |
| D/K | 0.2552 | likely_benign | 0.2701 | benign | 0.329 | Stabilizing | 0.157 | N | 0.396 | neutral | None | None | None | None | N |
| D/L | 0.4334 | ambiguous | 0.453 | ambiguous | 0.165 | Stabilizing | 0.567 | D | 0.483 | neutral | None | None | None | None | N |
| D/M | 0.6423 | likely_pathogenic | 0.6544 | pathogenic | -0.041 | Destabilizing | 0.968 | D | 0.505 | neutral | None | None | None | None | N |
| D/N | 0.0921 | likely_benign | 0.095 | benign | 0.216 | Stabilizing | 0.22 | N | 0.437 | neutral | N | 0.443165023 | None | None | N |
| D/P | 0.5872 | likely_pathogenic | 0.5845 | pathogenic | 0.149 | Stabilizing | 0.726 | D | 0.411 | neutral | None | None | None | None | N |
| D/Q | 0.2646 | likely_benign | 0.2744 | benign | 0.185 | Stabilizing | 0.396 | N | 0.379 | neutral | None | None | None | None | N |
| D/R | 0.3362 | likely_benign | 0.3348 | benign | 0.504 | Stabilizing | 0.396 | N | 0.453 | neutral | None | None | None | None | N |
| D/S | 0.1177 | likely_benign | 0.1236 | benign | 0.105 | Stabilizing | 0.157 | N | 0.403 | neutral | None | None | None | None | N |
| D/T | 0.259 | likely_benign | 0.2775 | benign | 0.162 | Stabilizing | 0.272 | N | 0.416 | neutral | None | None | None | None | N |
| D/V | 0.3038 | likely_benign | 0.314 | benign | 0.149 | Stabilizing | 0.497 | N | 0.461 | neutral | D | 0.546956627 | None | None | N |
| D/W | 0.8548 | likely_pathogenic | 0.8427 | pathogenic | -0.145 | Destabilizing | 0.968 | D | 0.626 | neutral | None | None | None | None | N |
| D/Y | 0.3109 | likely_benign | 0.3021 | benign | 0.074 | Stabilizing | 0.859 | D | 0.499 | neutral | D | 0.545471924 | 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.