Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3835 | 11728;11729;11730 | chr2:178741730;178741729;178741728 | chr2:179606457;179606456;179606455 |
| N2AB | 3518 | 10777;10778;10779 | chr2:178741730;178741729;178741728 | chr2:179606457;179606456;179606455 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3472 | 10639;10640;10641 | chr2:178741730;178741729;178741728 | chr2:179606457;179606456;179606455 |
| Novex-1 | 3597 | 11014;11015;11016 | chr2:178741730;178741729;178741728 | chr2:179606457;179606456;179606455 |
| Novex-2 | 3664 | 11215;11216;11217 | chr2:178741730;178741729;178741728 | chr2:179606457;179606456;179606455 |
| 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/G | rs1453631686  |
-0.69 | 0.989 | N | 0.518 | 0.386 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1303962639 |
0.088 | 1.0 | N | 0.707 | 0.351 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1303962639 |
0.088 | 1.0 | N | 0.707 | 0.351 | None | gnomAD-4.0.0 | 1.5915E-06 | None | None | None | None | N | None | 0 | 2.28739E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2382 | likely_benign | 0.2185 | benign | -0.567 | Destabilizing | 0.978 | D | 0.518 | neutral | N | 0.455551007 | None | None | N |
| D/C | 0.6688 | likely_pathogenic | 0.6583 | pathogenic | -0.023 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/E | 0.2349 | likely_benign | 0.2294 | benign | -0.328 | Destabilizing | 0.198 | N | 0.191 | neutral | N | 0.392598772 | None | None | N |
| D/F | 0.6603 | likely_pathogenic | 0.6417 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/G | 0.2532 | likely_benign | 0.2186 | benign | -0.783 | Destabilizing | 0.989 | D | 0.518 | neutral | N | 0.449232792 | None | None | N |
| D/H | 0.3312 | likely_benign | 0.3387 | benign | -0.434 | Destabilizing | 1.0 | D | 0.549 | neutral | N | 0.458492425 | None | None | N |
| D/I | 0.5342 | ambiguous | 0.5032 | ambiguous | -0.033 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/K | 0.4105 | ambiguous | 0.42 | ambiguous | 0.201 | Stabilizing | 0.967 | D | 0.512 | neutral | None | None | None | None | N |
| D/L | 0.5608 | ambiguous | 0.5376 | ambiguous | -0.033 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/M | 0.6902 | likely_pathogenic | 0.6622 | pathogenic | 0.268 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/N | 0.1023 | likely_benign | 0.1026 | benign | -0.172 | Destabilizing | 0.989 | D | 0.463 | neutral | N | 0.456089025 | None | None | N |
| D/P | 0.9512 | likely_pathogenic | 0.9301 | pathogenic | -0.189 | Destabilizing | 0.998 | D | 0.568 | neutral | None | None | None | None | N |
| D/Q | 0.4243 | ambiguous | 0.4338 | ambiguous | -0.127 | Destabilizing | 0.995 | D | 0.499 | neutral | None | None | None | None | N |
| D/R | 0.4514 | ambiguous | 0.4494 | ambiguous | 0.31 | Stabilizing | 0.995 | D | 0.651 | neutral | None | None | None | None | N |
| D/S | 0.1506 | likely_benign | 0.1433 | benign | -0.286 | Destabilizing | 0.983 | D | 0.397 | neutral | None | None | None | None | N |
| D/T | 0.3503 | ambiguous | 0.3221 | benign | -0.11 | Destabilizing | 0.998 | D | 0.521 | neutral | None | None | None | None | N |
| D/V | 0.3325 | likely_benign | 0.3041 | benign | -0.189 | Destabilizing | 0.997 | D | 0.707 | prob.neutral | N | 0.440718728 | None | None | N |
| D/W | 0.9091 | likely_pathogenic | 0.8995 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/Y | 0.244 | likely_benign | 0.2387 | benign | -0.205 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.460022527 | 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.