Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 974 | 3145;3146;3147 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| N2AB | 974 | 3145;3146;3147 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| N2A | 974 | 3145;3146;3147 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| N2B | 928 | 3007;3008;3009 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| Novex-1 | 928 | 3007;3008;3009 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| Novex-2 | 928 | 3007;3008;3009 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
| Novex-3 | 974 | 3145;3146;3147 | chr2:178782986;178782985;178782984 | chr2:179647713;179647712;179647711 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs749511236  |
None | 0.9 | N | 0.576 | 0.392 | 0.650309897564 | gnomAD-4.0.0 | 1.36816E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04032E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs749511236 |
-0.528 | 0.997 | D | 0.712 | 0.433 | 0.733702516443 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| V/M | rs749511236 |
-0.528 | 0.997 | D | 0.712 | 0.433 | 0.733702516443 | gnomAD-4.0.0 | 2.05224E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47794E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9189 | likely_pathogenic | 0.9348 | pathogenic | -1.577 | Destabilizing | 0.978 | D | 0.637 | neutral | D | 0.694997864 | None | None | N |
| V/C | 0.9919 | likely_pathogenic | 0.9924 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| V/D | 0.9984 | likely_pathogenic | 0.9989 | pathogenic | -1.34 | Destabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | N |
| V/E | 0.9923 | likely_pathogenic | 0.9948 | pathogenic | -1.221 | Destabilizing | 0.999 | D | 0.845 | deleterious | D | 0.731729316 | None | None | N |
| V/F | 0.91 | likely_pathogenic | 0.9278 | pathogenic | -0.992 | Destabilizing | 0.998 | D | 0.761 | deleterious | None | None | None | None | N |
| V/G | 0.9758 | likely_pathogenic | 0.983 | pathogenic | -2.029 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | D | 0.731729316 | None | None | N |
| V/H | 0.9986 | likely_pathogenic | 0.999 | pathogenic | -1.69 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| V/I | 0.1104 | likely_benign | 0.1109 | benign | -0.382 | Destabilizing | 0.437 | N | 0.212 | neutral | None | None | None | None | N |
| V/K | 0.9932 | likely_pathogenic | 0.9956 | pathogenic | -1.205 | Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | N |
| V/L | 0.7846 | likely_pathogenic | 0.8151 | pathogenic | -0.382 | Destabilizing | 0.9 | D | 0.576 | neutral | N | 0.517174595 | None | None | N |
| V/M | 0.7319 | likely_pathogenic | 0.7787 | pathogenic | -0.369 | Destabilizing | 0.997 | D | 0.712 | prob.delet. | D | 0.609596643 | None | None | N |
| V/N | 0.995 | likely_pathogenic | 0.9962 | pathogenic | -1.189 | Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| V/P | 0.9876 | likely_pathogenic | 0.9899 | pathogenic | -0.747 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| V/Q | 0.9931 | likely_pathogenic | 0.9952 | pathogenic | -1.151 | Destabilizing | 0.999 | D | 0.863 | deleterious | None | None | None | None | N |
| V/R | 0.991 | likely_pathogenic | 0.9939 | pathogenic | -0.983 | Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| V/S | 0.9837 | likely_pathogenic | 0.9876 | pathogenic | -1.842 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| V/T | 0.9318 | likely_pathogenic | 0.9394 | pathogenic | -1.579 | Destabilizing | 0.992 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/W | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -1.333 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| V/Y | 0.995 | likely_pathogenic | 0.9964 | pathogenic | -0.959 | Destabilizing | 0.999 | D | 0.757 | deleterious | 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.