Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30151 | 90676;90677;90678 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| N2AB | 28510 | 85753;85754;85755 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| N2A | 27583 | 82972;82973;82974 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| N2B | 21086 | 63481;63482;63483 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| Novex-1 | 21211 | 63856;63857;63858 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| Novex-2 | 21278 | 64057;64058;64059 | chr2:178552449;178552448;178552447 | chr2:179417176;179417175;179417174 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs750520740  |
-1.379 | 0.934 | D | 0.695 | 0.315 | 0.567605623258 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs750520740 |
-1.379 | 0.934 | D | 0.695 | 0.315 | 0.567605623258 | gnomAD-4.0.0 | 3.22724E-06 | None | None | None | None | N | None | 0 | 2.2979E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.06147E-05 |
| L/P | rs568322187 |
-1.457 | 0.966 | D | 0.843 | 0.757 | 0.8955048179 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.36E-05 | 0 |
| L/P | rs568322187 |
-1.457 | 0.966 | D | 0.843 | 0.757 | 0.8955048179 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| L/P | rs568322187 |
-1.457 | 0.966 | D | 0.843 | 0.757 | 0.8955048179 | gnomAD-4.0.0 | 6.16875E-05 | None | None | None | None | N | None | 2.67437E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.18452E-05 | 0 | 1.61197E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7132 | likely_pathogenic | 0.6419 | pathogenic | -2.38 | Highly Destabilizing | 0.016 | N | 0.515 | neutral | None | None | None | None | N |
| L/C | 0.7442 | likely_pathogenic | 0.6715 | pathogenic | -1.822 | Destabilizing | 0.998 | D | 0.752 | deleterious | None | None | None | None | N |
| L/D | 0.9935 | likely_pathogenic | 0.9902 | pathogenic | -1.972 | Destabilizing | 0.974 | D | 0.842 | deleterious | None | None | None | None | N |
| L/E | 0.9612 | likely_pathogenic | 0.9496 | pathogenic | -1.796 | Destabilizing | 0.949 | D | 0.827 | deleterious | None | None | None | None | N |
| L/F | 0.2766 | likely_benign | 0.1939 | benign | -1.424 | Destabilizing | 0.934 | D | 0.695 | prob.neutral | D | 0.532539469 | None | None | N |
| L/G | 0.9557 | likely_pathogenic | 0.9379 | pathogenic | -2.857 | Highly Destabilizing | 0.904 | D | 0.811 | deleterious | None | None | None | None | N |
| L/H | 0.894 | likely_pathogenic | 0.8346 | pathogenic | -1.868 | Destabilizing | 0.997 | D | 0.827 | deleterious | D | 0.613826835 | None | None | N |
| L/I | 0.0957 | likely_benign | 0.0851 | benign | -1.034 | Destabilizing | 0.005 | N | 0.293 | neutral | D | 0.531397599 | None | None | N |
| L/K | 0.9299 | likely_pathogenic | 0.8959 | pathogenic | -1.867 | Destabilizing | 0.949 | D | 0.793 | deleterious | None | None | None | None | N |
| L/M | 0.1608 | likely_benign | 0.1424 | benign | -1.026 | Destabilizing | 0.949 | D | 0.668 | neutral | None | None | None | None | N |
| L/N | 0.9688 | likely_pathogenic | 0.9542 | pathogenic | -2.075 | Highly Destabilizing | 0.974 | D | 0.841 | deleterious | None | None | None | None | N |
| L/P | 0.9776 | likely_pathogenic | 0.9765 | pathogenic | -1.46 | Destabilizing | 0.966 | D | 0.843 | deleterious | D | 0.613826835 | None | None | N |
| L/Q | 0.8735 | likely_pathogenic | 0.831 | pathogenic | -1.995 | Destabilizing | 0.974 | D | 0.817 | deleterious | None | None | None | None | N |
| L/R | 0.8874 | likely_pathogenic | 0.8471 | pathogenic | -1.472 | Destabilizing | 0.966 | D | 0.826 | deleterious | D | 0.613826835 | None | None | N |
| L/S | 0.9264 | likely_pathogenic | 0.8858 | pathogenic | -2.825 | Highly Destabilizing | 0.728 | D | 0.785 | deleterious | None | None | None | None | N |
| L/T | 0.7087 | likely_pathogenic | 0.6535 | pathogenic | -2.49 | Highly Destabilizing | 0.842 | D | 0.704 | prob.neutral | None | None | None | None | N |
| L/V | 0.1149 | likely_benign | 0.1061 | benign | -1.46 | Destabilizing | 0.012 | N | 0.379 | neutral | D | 0.548508205 | None | None | N |
| L/W | 0.6854 | likely_pathogenic | 0.5904 | pathogenic | -1.539 | Destabilizing | 0.998 | D | 0.804 | deleterious | None | None | None | None | N |
| L/Y | 0.7868 | likely_pathogenic | 0.6824 | pathogenic | -1.338 | Destabilizing | 0.974 | D | 0.764 | 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.