Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23578 | 70957;70958;70959 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| N2AB | 21937 | 66034;66035;66036 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| N2A | 21010 | 63253;63254;63255 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| N2B | 14513 | 43762;43763;43764 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| Novex-1 | 14638 | 44137;44138;44139 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| Novex-2 | 14705 | 44338;44339;44340 | chr2:178575400;178575399;178575398 | chr2:179440127;179440126;179440125 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/H | rs1342674248  |
-0.281 | 0.009 | N | 0.305 | 0.069 | 0.166414681773 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| Q/H | rs1342674248 |
-0.281 | 0.009 | N | 0.305 | 0.069 | 0.166414681773 | gnomAD-4.0.0 | 1.59176E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8591E-06 | 0 | 0 |
| Q/R | rs1332842062 |
0.471 | 0.379 | N | 0.309 | 0.196 | 0.191931220699 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Q/R | rs1332842062 |
0.471 | 0.379 | N | 0.309 | 0.196 | 0.191931220699 | gnomAD-4.0.0 | 1.59175E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1904 | likely_benign | 0.2029 | benign | -0.105 | Destabilizing | 0.4 | N | 0.342 | neutral | None | None | None | None | N |
| Q/C | 0.537 | ambiguous | 0.5665 | pathogenic | 0.108 | Stabilizing | 0.992 | D | 0.403 | neutral | None | None | None | None | N |
| Q/D | 0.3365 | likely_benign | 0.347 | ambiguous | -0.025 | Destabilizing | 0.005 | N | 0.193 | neutral | None | None | None | None | N |
| Q/E | 0.0893 | likely_benign | 0.0901 | benign | -0.078 | Destabilizing | 0.201 | N | 0.327 | neutral | N | 0.419565388 | None | None | N |
| Q/F | 0.5894 | likely_pathogenic | 0.619 | pathogenic | -0.461 | Destabilizing | 0.85 | D | 0.377 | neutral | None | None | None | None | N |
| Q/G | 0.2667 | likely_benign | 0.2786 | benign | -0.233 | Destabilizing | 0.617 | D | 0.346 | neutral | None | None | None | None | N |
| Q/H | 0.1546 | likely_benign | 0.1668 | benign | -0.065 | Destabilizing | 0.009 | N | 0.305 | neutral | N | 0.481598069 | None | None | N |
| Q/I | 0.2619 | likely_benign | 0.2757 | benign | 0.137 | Stabilizing | 0.92 | D | 0.379 | neutral | None | None | None | None | N |
| Q/K | 0.0781 | likely_benign | 0.0827 | benign | 0.086 | Stabilizing | 0.016 | N | 0.194 | neutral | N | 0.394459087 | None | None | N |
| Q/L | 0.1242 | likely_benign | 0.1325 | benign | 0.137 | Stabilizing | 0.549 | D | 0.359 | neutral | N | 0.476498893 | None | None | N |
| Q/M | 0.2973 | likely_benign | 0.3083 | benign | 0.23 | Stabilizing | 0.972 | D | 0.295 | neutral | None | None | None | None | N |
| Q/N | 0.2313 | likely_benign | 0.2423 | benign | -0.093 | Destabilizing | 0.447 | N | 0.287 | neutral | None | None | None | None | N |
| Q/P | 0.3875 | ambiguous | 0.3921 | ambiguous | 0.081 | Stabilizing | 0.896 | D | 0.311 | neutral | N | 0.508629954 | None | None | N |
| Q/R | 0.0871 | likely_benign | 0.0912 | benign | 0.28 | Stabilizing | 0.379 | N | 0.309 | neutral | N | 0.458105134 | None | None | N |
| Q/S | 0.2091 | likely_benign | 0.2148 | benign | -0.107 | Destabilizing | 0.617 | D | 0.326 | neutral | None | None | None | None | N |
| Q/T | 0.1462 | likely_benign | 0.1496 | benign | -0.029 | Destabilizing | 0.617 | D | 0.341 | neutral | None | None | None | None | N |
| Q/V | 0.1804 | likely_benign | 0.1888 | benign | 0.081 | Stabilizing | 0.766 | D | 0.355 | neutral | None | None | None | None | N |
| Q/W | 0.5678 | likely_pathogenic | 0.5692 | pathogenic | -0.509 | Destabilizing | 0.992 | D | 0.417 | neutral | None | None | None | None | N |
| Q/Y | 0.39 | ambiguous | 0.4001 | ambiguous | -0.225 | Destabilizing | 0.739 | D | 0.315 | 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.