Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31382 | 94369;94370;94371 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| N2AB | 29741 | 89446;89447;89448 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| N2A | 28814 | 86665;86666;86667 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| N2B | 22317 | 67174;67175;67176 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| Novex-1 | 22442 | 67549;67550;67551 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| Novex-2 | 22509 | 67750;67751;67752 | chr2:178547482;178547481;178547480 | chr2:179412209;179412208;179412207 |
| 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/C | rs761156972  |
-1.546 | 1.0 | D | 0.733 | 0.472 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| R/C | rs761156972 |
-1.546 | 1.0 | D | 0.733 | 0.472 | None | 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/C | rs761156972 |
-1.546 | 1.0 | D | 0.733 | 0.472 | None | gnomAD-4.0.0 | 4.34113E-06 | None | None | None | None | N | None | 2.67101E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39192E-06 | 1.09946E-05 | 0 |
| R/H | rs775769975 |
-2.09 | 0.998 | D | 0.579 | 0.498 | 0.481099667738 | gnomAD-2.1.1 | 7.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.08138E-04 | None | 6.58E-05 | None | 1.6063E-04 | 6.32E-05 | 2.8401E-04 |
| R/H | rs775769975 |
-2.09 | 0.998 | D | 0.579 | 0.498 | 0.481099667738 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85208E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs775769975 |
-2.09 | 0.998 | D | 0.579 | 0.498 | 0.481099667738 | gnomAD-4.0.0 | 4.4649E-05 | None | None | None | None | N | None | 2.66581E-05 | 0 | None | 0 | 1.11832E-04 | None | 1.5648E-04 | 0 | 3.90105E-05 | 4.39773E-05 | 8.00897E-05 |
| R/L | None | None | 0.988 | N | 0.597 | 0.544 | 0.750867034168 | gnomAD-4.0.0 | 6.84793E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16104E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9831 | likely_pathogenic | 0.9836 | pathogenic | -1.639 | Destabilizing | 0.754 | D | 0.591 | neutral | None | None | None | None | N |
| R/C | 0.6413 | likely_pathogenic | 0.6664 | pathogenic | -1.617 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.5277396 | None | None | N |
| R/D | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -0.84 | Destabilizing | 0.956 | D | 0.598 | neutral | None | None | None | None | N |
| R/E | 0.9824 | likely_pathogenic | 0.985 | pathogenic | -0.637 | Destabilizing | 0.926 | D | 0.553 | neutral | None | None | None | None | N |
| R/F | 0.9912 | likely_pathogenic | 0.9924 | pathogenic | -0.847 | Destabilizing | 0.993 | D | 0.74 | deleterious | None | None | None | None | N |
| R/G | 0.9833 | likely_pathogenic | 0.9845 | pathogenic | -1.974 | Destabilizing | 0.036 | N | 0.531 | neutral | D | 0.53423406 | None | None | N |
| R/H | 0.6033 | likely_pathogenic | 0.6379 | pathogenic | -1.931 | Destabilizing | 0.998 | D | 0.579 | neutral | D | 0.545843855 | None | None | N |
| R/I | 0.9613 | likely_pathogenic | 0.9682 | pathogenic | -0.678 | Destabilizing | 0.978 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/K | 0.5202 | ambiguous | 0.532 | ambiguous | -1.235 | Destabilizing | 0.717 | D | 0.622 | neutral | None | None | None | None | N |
| R/L | 0.928 | likely_pathogenic | 0.9405 | pathogenic | -0.678 | Destabilizing | 0.988 | D | 0.597 | neutral | N | 0.511610355 | None | None | N |
| R/M | 0.9668 | likely_pathogenic | 0.9723 | pathogenic | -1.223 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| R/N | 0.9958 | likely_pathogenic | 0.9964 | pathogenic | -1.168 | Destabilizing | 0.956 | D | 0.535 | neutral | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -0.986 | Destabilizing | 0.996 | D | 0.681 | prob.neutral | D | 0.546097345 | None | None | N |
| R/Q | 0.5331 | ambiguous | 0.5524 | ambiguous | -0.991 | Destabilizing | 0.993 | D | 0.515 | neutral | None | None | None | None | N |
| R/S | 0.9899 | likely_pathogenic | 0.9908 | pathogenic | -1.942 | Destabilizing | 0.922 | D | 0.551 | neutral | D | 0.542295002 | None | None | N |
| R/T | 0.9822 | likely_pathogenic | 0.9848 | pathogenic | -1.541 | Destabilizing | 0.978 | D | 0.556 | neutral | None | None | None | None | N |
| R/V | 0.9689 | likely_pathogenic | 0.9707 | pathogenic | -0.986 | Destabilizing | 0.978 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/W | 0.8653 | likely_pathogenic | 0.8976 | pathogenic | -0.472 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/Y | 0.9743 | likely_pathogenic | 0.9773 | pathogenic | -0.287 | Destabilizing | 0.993 | D | 0.704 | 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.