Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7644 | 23155;23156;23157 | chr2:178721089;178721088;178721087 | chr2:179585816;179585815;179585814 |
| N2AB | 7327 | 22204;22205;22206 | chr2:178721089;178721088;178721087 | chr2:179585816;179585815;179585814 |
| N2A | 6400 | 19423;19424;19425 | chr2:178721089;178721088;178721087 | chr2:179585816;179585815;179585814 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs766675017  |
-1.405 | 0.958 | N | 0.537 | 0.154 | 0.158396225186 | gnomAD-2.1.1 | 7.86E-05 | None | None | None | None | N | None | 0 | 4.52822E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.92E-05 | 0 |
| R/Q | rs766675017 |
-1.405 | 0.958 | N | 0.537 | 0.154 | 0.158396225186 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs766675017 |
-1.405 | 0.958 | N | 0.537 | 0.154 | 0.158396225186 | gnomAD-4.0.0 | 2.23175E-05 | None | None | None | None | N | None | 1.33533E-05 | 2.50083E-04 | None | 3.38043E-05 | 0 | None | 0 | 0 | 1.35672E-05 | 1.09851E-05 | 3.20379E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5702 | likely_pathogenic | 0.6676 | pathogenic | -2.013 | Highly Destabilizing | 0.688 | D | 0.517 | neutral | None | None | None | None | N |
| R/C | 0.1724 | likely_benign | 0.205 | benign | -1.983 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| R/D | 0.9101 | likely_pathogenic | 0.941 | pathogenic | -0.704 | Destabilizing | 0.842 | D | 0.572 | neutral | None | None | None | None | N |
| R/E | 0.5438 | ambiguous | 0.6415 | pathogenic | -0.537 | Destabilizing | 0.525 | D | 0.539 | neutral | None | None | None | None | N |
| R/F | 0.6642 | likely_pathogenic | 0.7416 | pathogenic | -1.796 | Destabilizing | 0.991 | D | 0.629 | neutral | None | None | None | None | N |
| R/G | 0.5356 | ambiguous | 0.6153 | pathogenic | -2.334 | Highly Destabilizing | 0.911 | D | 0.535 | neutral | N | 0.508274877 | None | None | N |
| R/H | 0.129 | likely_benign | 0.143 | benign | -2.422 | Highly Destabilizing | 0.991 | D | 0.523 | neutral | None | None | None | None | N |
| R/I | 0.2745 | likely_benign | 0.388 | ambiguous | -1.103 | Destabilizing | 0.974 | D | 0.617 | neutral | None | None | None | None | N |
| R/K | 0.0906 | likely_benign | 0.0987 | benign | -1.593 | Destabilizing | 0.002 | N | 0.144 | neutral | None | None | None | None | N |
| R/L | 0.2438 | likely_benign | 0.3288 | benign | -1.103 | Destabilizing | 0.911 | D | 0.535 | neutral | N | 0.44647427 | None | None | N |
| R/M | 0.3216 | likely_benign | 0.4048 | ambiguous | -1.276 | Destabilizing | 0.991 | D | 0.577 | neutral | None | None | None | None | N |
| R/N | 0.7946 | likely_pathogenic | 0.8489 | pathogenic | -1.248 | Destabilizing | 0.842 | D | 0.512 | neutral | None | None | None | None | N |
| R/P | 0.964 | likely_pathogenic | 0.9772 | pathogenic | -1.392 | Destabilizing | 0.986 | D | 0.597 | neutral | N | 0.479155648 | None | None | N |
| R/Q | 0.1071 | likely_benign | 0.1205 | benign | -1.386 | Destabilizing | 0.958 | D | 0.537 | neutral | N | 0.497153806 | None | None | N |
| R/S | 0.6837 | likely_pathogenic | 0.7491 | pathogenic | -2.306 | Highly Destabilizing | 0.842 | D | 0.507 | neutral | None | None | None | None | N |
| R/T | 0.4993 | ambiguous | 0.6002 | pathogenic | -1.927 | Destabilizing | 0.842 | D | 0.516 | neutral | None | None | None | None | N |
| R/V | 0.3922 | ambiguous | 0.5166 | ambiguous | -1.392 | Destabilizing | 0.974 | D | 0.599 | neutral | None | None | None | None | N |
| R/W | 0.2281 | likely_benign | 0.27 | benign | -1.258 | Destabilizing | 0.998 | D | 0.66 | neutral | None | None | None | None | N |
| R/Y | 0.4905 | ambiguous | 0.5842 | pathogenic | -1.069 | Destabilizing | 0.991 | D | 0.599 | 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.