Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25455 | 76588;76589;76590 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| N2AB | 23814 | 71665;71666;71667 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| N2A | 22887 | 68884;68885;68886 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| N2B | 16390 | 49393;49394;49395 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| Novex-1 | 16515 | 49768;49769;49770 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| Novex-2 | 16582 | 49969;49970;49971 | chr2:178569769;178569768;178569767 | chr2:179434496;179434495;179434494 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs1179441245  |
-1.113 | 0.99 | N | 0.738 | 0.413 | 0.613315917884 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| C/Y | rs1179441245 |
-1.113 | 0.99 | N | 0.738 | 0.413 | 0.613315917884 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/Y | rs1179441245 |
-1.113 | 0.99 | N | 0.738 | 0.413 | 0.613315917884 | gnomAD-4.0.0 | 5.12863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57657E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4484 | ambiguous | 0.4459 | ambiguous | -1.602 | Destabilizing | 0.559 | D | 0.407 | neutral | None | None | None | None | N |
| C/D | 0.8365 | likely_pathogenic | 0.8158 | pathogenic | -0.289 | Destabilizing | 0.956 | D | 0.711 | prob.delet. | None | None | None | None | N |
| C/E | 0.8929 | likely_pathogenic | 0.88 | pathogenic | -0.208 | Destabilizing | 0.956 | D | 0.729 | prob.delet. | None | None | None | None | N |
| C/F | 0.2915 | likely_benign | 0.2961 | benign | -1.016 | Destabilizing | 0.97 | D | 0.734 | prob.delet. | N | 0.465550255 | None | None | N |
| C/G | 0.3596 | ambiguous | 0.3344 | benign | -1.892 | Destabilizing | 0.698 | D | 0.629 | neutral | N | 0.470425327 | None | None | N |
| C/H | 0.7286 | likely_pathogenic | 0.7023 | pathogenic | -1.881 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| C/I | 0.3456 | ambiguous | 0.3624 | ambiguous | -0.868 | Destabilizing | 0.978 | D | 0.619 | neutral | None | None | None | None | N |
| C/K | 0.9427 | likely_pathogenic | 0.9357 | pathogenic | -0.967 | Destabilizing | 0.956 | D | 0.699 | prob.neutral | None | None | None | None | N |
| C/L | 0.4265 | ambiguous | 0.4568 | ambiguous | -0.868 | Destabilizing | 0.86 | D | 0.488 | neutral | None | None | None | None | N |
| C/M | 0.6417 | likely_pathogenic | 0.65 | pathogenic | 0.012 | Stabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| C/N | 0.6715 | likely_pathogenic | 0.6605 | pathogenic | -0.882 | Destabilizing | 0.956 | D | 0.73 | prob.delet. | None | None | None | None | N |
| C/P | 0.9632 | likely_pathogenic | 0.965 | pathogenic | -1.087 | Destabilizing | 0.978 | D | 0.763 | deleterious | None | None | None | None | N |
| C/Q | 0.8174 | likely_pathogenic | 0.7935 | pathogenic | -0.825 | Destabilizing | 0.956 | D | 0.772 | deleterious | None | None | None | None | N |
| C/R | 0.7738 | likely_pathogenic | 0.756 | pathogenic | -0.762 | Destabilizing | 0.942 | D | 0.769 | deleterious | N | 0.47888157 | None | None | N |
| C/S | 0.3861 | ambiguous | 0.3619 | ambiguous | -1.42 | Destabilizing | 0.058 | N | 0.371 | neutral | N | 0.47213362 | None | None | N |
| C/T | 0.5377 | ambiguous | 0.5305 | ambiguous | -1.164 | Destabilizing | 0.754 | D | 0.515 | neutral | None | None | None | None | N |
| C/V | 0.2912 | likely_benign | 0.3001 | benign | -1.087 | Destabilizing | 0.86 | D | 0.553 | neutral | None | None | None | None | N |
| C/W | 0.7263 | likely_pathogenic | 0.7048 | pathogenic | -0.991 | Destabilizing | 0.997 | D | 0.725 | prob.delet. | N | 0.502608139 | None | None | N |
| C/Y | 0.434 | ambiguous | 0.4391 | ambiguous | -0.985 | Destabilizing | 0.99 | D | 0.738 | prob.delet. | N | 0.479135059 | 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.