Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24647 | 74164;74165;74166 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| N2AB | 23006 | 69241;69242;69243 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| N2A | 22079 | 66460;66461;66462 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| N2B | 15582 | 46969;46970;46971 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| Novex-1 | 15707 | 47344;47345;47346 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| Novex-2 | 15774 | 47545;47546;47547 | chr2:178572193;178572192;178572191 | chr2:179436920;179436919;179436918 |
| 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 | rs767512581  |
0.181 | 0.992 | N | 0.598 | 0.255 | 0.216624796971 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.48E-05 | 0 |
| R/Q | rs767512581 |
0.181 | 0.992 | N | 0.598 | 0.255 | 0.216624796971 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs767512581 |
0.181 | 0.992 | N | 0.598 | 0.255 | 0.216624796971 | gnomAD-4.0.0 | 2.54132E-05 | None | None | None | None | N | None | 4.00566E-05 | 3.33533E-05 | None | 0 | 0 | None | 0 | 0 | 2.37363E-05 | 1.09798E-05 | 1.12097E-04 |
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 | 0.9396 | likely_pathogenic | 0.9155 | pathogenic | -0.015 | Destabilizing | 0.847 | D | 0.609 | neutral | None | None | None | None | N |
| R/C | 0.7745 | likely_pathogenic | 0.6813 | pathogenic | -0.135 | Destabilizing | 0.998 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/D | 0.9834 | likely_pathogenic | 0.978 | pathogenic | -0.021 | Destabilizing | 0.975 | D | 0.631 | neutral | None | None | None | None | N |
| R/E | 0.9445 | likely_pathogenic | 0.9264 | pathogenic | 0.066 | Stabilizing | 0.625 | D | 0.599 | neutral | None | None | None | None | N |
| R/F | 0.9667 | likely_pathogenic | 0.9511 | pathogenic | -0.122 | Destabilizing | 0.994 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/G | 0.9126 | likely_pathogenic | 0.8813 | pathogenic | -0.246 | Destabilizing | 0.914 | D | 0.587 | neutral | N | 0.476248177 | None | None | N |
| R/H | 0.4809 | ambiguous | 0.4034 | ambiguous | -0.766 | Destabilizing | 0.98 | D | 0.596 | neutral | None | None | None | None | N |
| R/I | 0.8832 | likely_pathogenic | 0.8318 | pathogenic | 0.567 | Stabilizing | 0.942 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/K | 0.2462 | likely_benign | 0.2307 | benign | -0.06 | Destabilizing | 0.215 | N | 0.529 | neutral | None | None | None | None | N |
| R/L | 0.8488 | likely_pathogenic | 0.8056 | pathogenic | 0.567 | Stabilizing | 0.815 | D | 0.578 | neutral | N | 0.47382432 | None | None | N |
| R/M | 0.91 | likely_pathogenic | 0.8699 | pathogenic | 0.059 | Stabilizing | 0.995 | D | 0.615 | neutral | None | None | None | None | N |
| R/N | 0.9759 | likely_pathogenic | 0.9651 | pathogenic | 0.176 | Stabilizing | 0.975 | D | 0.583 | neutral | None | None | None | None | N |
| R/P | 0.901 | likely_pathogenic | 0.8728 | pathogenic | 0.395 | Stabilizing | 0.032 | N | 0.483 | neutral | N | 0.412713987 | None | None | N |
| R/Q | 0.594 | likely_pathogenic | 0.5032 | ambiguous | 0.103 | Stabilizing | 0.992 | D | 0.598 | neutral | N | 0.490812198 | None | None | N |
| R/S | 0.9735 | likely_pathogenic | 0.962 | pathogenic | -0.207 | Destabilizing | 0.847 | D | 0.599 | neutral | None | None | None | None | N |
| R/T | 0.9385 | likely_pathogenic | 0.91 | pathogenic | 0.03 | Stabilizing | 0.847 | D | 0.592 | neutral | None | None | None | None | N |
| R/V | 0.8994 | likely_pathogenic | 0.8621 | pathogenic | 0.395 | Stabilizing | 0.922 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/W | 0.745 | likely_pathogenic | 0.671 | pathogenic | -0.13 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| R/Y | 0.9059 | likely_pathogenic | 0.8707 | pathogenic | 0.267 | Stabilizing | 0.979 | D | 0.707 | prob.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.