Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24954 | 75085;75086;75087 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| N2AB | 23313 | 70162;70163;70164 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| N2A | 22386 | 67381;67382;67383 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| N2B | 15889 | 47890;47891;47892 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| Novex-1 | 16014 | 48265;48266;48267 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| Novex-2 | 16081 | 48466;48467;48468 | chr2:178571272;178571271;178571270 | chr2:179435999;179435998;179435997 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs202191466  |
-0.557 | 1.0 | N | 0.585 | 0.32 | 0.586602809486 | gnomAD-2.1.1 | 1.12726E-04 | None | None | None | None | I | None | 0 | 6.95612E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 1.65893E-04 |
| L/F | rs202191466 |
-0.557 | 1.0 | N | 0.585 | 0.32 | 0.586602809486 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs202191466 |
-0.557 | 1.0 | N | 0.585 | 0.32 | 0.586602809486 | gnomAD-4.0.0 | 2.47937E-05 | None | None | None | None | I | None | 0 | 4.5039E-04 | None | 0 | 0 | None | 0 | 0 | 8.47719E-06 | 1.09798E-05 | 3.20318E-05 |
| L/P | None | None | 1.0 | N | 0.735 | 0.569 | 0.810833939436 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8194 | likely_pathogenic | 0.7941 | pathogenic | -0.768 | Destabilizing | 0.999 | D | 0.549 | neutral | None | None | None | None | I |
| L/C | 0.8761 | likely_pathogenic | 0.8626 | pathogenic | -0.718 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| L/D | 0.988 | likely_pathogenic | 0.9846 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| L/E | 0.9406 | likely_pathogenic | 0.9271 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| L/F | 0.5238 | ambiguous | 0.5215 | ambiguous | -0.595 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.479940386 | None | None | I |
| L/G | 0.9476 | likely_pathogenic | 0.9386 | pathogenic | -0.959 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| L/H | 0.7661 | likely_pathogenic | 0.7457 | pathogenic | -0.05 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.469963206 | None | None | I |
| L/I | 0.2118 | likely_benign | 0.2019 | benign | -0.365 | Destabilizing | 0.999 | D | 0.482 | neutral | N | 0.477711887 | None | None | I |
| L/K | 0.8454 | likely_pathogenic | 0.8266 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| L/M | 0.2503 | likely_benign | 0.2463 | benign | -0.579 | Destabilizing | 1.0 | D | 0.547 | neutral | None | None | None | None | I |
| L/N | 0.8885 | likely_pathogenic | 0.8674 | pathogenic | -0.355 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| L/P | 0.9617 | likely_pathogenic | 0.9647 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.472343063 | None | None | I |
| L/Q | 0.6782 | likely_pathogenic | 0.648 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| L/R | 0.6974 | likely_pathogenic | 0.686 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.443482398 | None | None | I |
| L/S | 0.8805 | likely_pathogenic | 0.8598 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| L/T | 0.7772 | likely_pathogenic | 0.7236 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | I |
| L/V | 0.3084 | likely_benign | 0.2804 | benign | -0.468 | Destabilizing | 0.999 | D | 0.533 | neutral | N | 0.516364003 | None | None | I |
| L/W | 0.7771 | likely_pathogenic | 0.7856 | pathogenic | -0.616 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| L/Y | 0.8074 | likely_pathogenic | 0.8034 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
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.