Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28484 | 85675;85676;85677 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| N2AB | 26843 | 80752;80753;80754 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| N2A | 25916 | 77971;77972;77973 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| N2B | 19419 | 58480;58481;58482 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| Novex-1 | 19544 | 58855;58856;58857 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| Novex-2 | 19611 | 59056;59057;59058 | chr2:178560682;178560681;178560680 | chr2:179425409;179425408;179425407 |
| 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/E | rs768596884  |
-0.44 | 0.835 | N | 0.394 | 0.157 | 0.15556083564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/E | rs768596884 |
-0.44 | 0.835 | N | 0.394 | 0.157 | 0.15556083564 | gnomAD-4.0.0 | 6.8429E-07 | None | None | None | None | N | None | 0 | 0 | None | 3.82702E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | None | -0.816 | 0.996 | N | 0.481 | 0.253 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 2.06885E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| D/N | None | -0.816 | 0.996 | N | 0.481 | 0.253 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 2.17307E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | None | -0.816 | 0.996 | N | 0.481 | 0.253 | None | gnomAD-4.0.0 | 3.34689E-05 | None | None | None | None | N | None | 2.80441E-04 | 1.66822E-05 | None | 0 | 0 | None | 0 | 0 | 2.54285E-05 | 0 | 3.20256E-05 |
| D/Y | rs56330345 |
-0.069 | 0.999 | N | 0.568 | 0.315 | 0.610467662648 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/Y | rs56330345 |
-0.069 | 0.999 | N | 0.568 | 0.315 | 0.610467662648 | gnomAD-4.0.0 | 1.42553E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.94952E-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 | 0.1096 | likely_benign | 0.1081 | benign | -0.596 | Destabilizing | 0.961 | D | 0.443 | neutral | N | 0.473845377 | None | None | N |
| D/C | 0.4262 | ambiguous | 0.4417 | ambiguous | -0.357 | Destabilizing | 1.0 | D | 0.584 | neutral | None | None | None | None | N |
| D/E | 0.1417 | likely_benign | 0.1399 | benign | -0.516 | Destabilizing | 0.835 | D | 0.394 | neutral | N | 0.389997417 | None | None | N |
| D/F | 0.4718 | ambiguous | 0.479 | ambiguous | -0.142 | Destabilizing | 0.991 | D | 0.572 | neutral | None | None | None | None | N |
| D/G | 0.1435 | likely_benign | 0.1379 | benign | -0.894 | Destabilizing | 0.98 | D | 0.397 | neutral | N | 0.462399019 | None | None | N |
| D/H | 0.1751 | likely_benign | 0.18 | benign | -0.191 | Destabilizing | 0.999 | D | 0.525 | neutral | N | 0.518425661 | None | None | N |
| D/I | 0.2238 | likely_benign | 0.2332 | benign | 0.179 | Stabilizing | 0.983 | D | 0.471 | neutral | None | None | None | None | N |
| D/K | 0.2122 | likely_benign | 0.2223 | benign | -0.383 | Destabilizing | 0.942 | D | 0.399 | neutral | None | None | None | None | N |
| D/L | 0.2236 | likely_benign | 0.236 | benign | 0.179 | Stabilizing | 0.871 | D | 0.498 | neutral | None | None | None | None | N |
| D/M | 0.447 | ambiguous | 0.4591 | ambiguous | 0.411 | Stabilizing | 0.559 | D | 0.343 | neutral | None | None | None | None | N |
| D/N | 0.0818 | likely_benign | 0.083 | benign | -0.779 | Destabilizing | 0.996 | D | 0.481 | neutral | N | 0.474365452 | None | None | N |
| D/P | 0.728 | likely_pathogenic | 0.7264 | pathogenic | -0.056 | Destabilizing | 0.999 | D | 0.491 | neutral | None | None | None | None | N |
| D/Q | 0.2213 | likely_benign | 0.2267 | benign | -0.663 | Destabilizing | 0.746 | D | 0.199 | neutral | None | None | None | None | N |
| D/R | 0.2333 | likely_benign | 0.2435 | benign | -0.061 | Destabilizing | 0.991 | D | 0.466 | neutral | None | None | None | None | N |
| D/S | 0.0834 | likely_benign | 0.0817 | benign | -0.968 | Destabilizing | 0.97 | D | 0.379 | neutral | None | None | None | None | N |
| D/T | 0.1272 | likely_benign | 0.1299 | benign | -0.73 | Destabilizing | 0.985 | D | 0.432 | neutral | None | None | None | None | N |
| D/V | 0.1472 | likely_benign | 0.1516 | benign | -0.056 | Destabilizing | 0.925 | D | 0.475 | neutral | N | 0.460665436 | None | None | N |
| D/W | 0.8189 | likely_pathogenic | 0.8306 | pathogenic | 0.085 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| D/Y | 0.151 | likely_benign | 0.1572 | benign | 0.089 | Stabilizing | 0.999 | D | 0.568 | neutral | N | 0.4998399 | 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.