Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25655 | 77188;77189;77190 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| N2AB | 24014 | 72265;72266;72267 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| N2A | 23087 | 69484;69485;69486 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| N2B | 16590 | 49993;49994;49995 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| Novex-1 | 16715 | 50368;50369;50370 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| Novex-2 | 16782 | 50569;50570;50571 | chr2:178569169;178569168;178569167 | chr2:179433896;179433895;179433894 |
| 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/R | rs752535050  |
-1.593 | 0.923 | N | 0.568 | 0.466 | 0.731068662627 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.64669E-04 | None | 0 | 0 | 0 |
| C/R | rs752535050 |
-1.593 | 0.923 | N | 0.568 | 0.466 | 0.731068662627 | gnomAD-4.0.0 | 8.21389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.39395E-04 | 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 | 0.7782 | likely_pathogenic | 0.7794 | pathogenic | -1.501 | Destabilizing | 0.89 | D | 0.604 | neutral | None | None | None | None | N |
| C/D | 0.989 | likely_pathogenic | 0.9887 | pathogenic | -1.468 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| C/E | 0.9929 | likely_pathogenic | 0.992 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| C/F | 0.7252 | likely_pathogenic | 0.7378 | pathogenic | -0.926 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.494535468 | None | None | N |
| C/G | 0.6448 | likely_pathogenic | 0.6463 | pathogenic | -1.861 | Destabilizing | 0.974 | D | 0.739 | prob.delet. | N | 0.500354401 | None | None | N |
| C/H | 0.9411 | likely_pathogenic | 0.9459 | pathogenic | -2.149 | Highly Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| C/I | 0.7126 | likely_pathogenic | 0.7199 | pathogenic | -0.521 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/K | 0.9946 | likely_pathogenic | 0.994 | pathogenic | -0.94 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| C/L | 0.7554 | likely_pathogenic | 0.753 | pathogenic | -0.521 | Destabilizing | 0.995 | D | 0.617 | neutral | None | None | None | None | N |
| C/M | 0.8758 | likely_pathogenic | 0.8723 | pathogenic | 0.387 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| C/N | 0.8834 | likely_pathogenic | 0.8806 | pathogenic | -1.606 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| C/P | 0.9868 | likely_pathogenic | 0.9854 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| C/Q | 0.9686 | likely_pathogenic | 0.9662 | pathogenic | -1.083 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| C/R | 0.9607 | likely_pathogenic | 0.959 | pathogenic | -1.476 | Destabilizing | 0.923 | D | 0.568 | neutral | N | 0.487191634 | None | None | N |
| C/S | 0.6433 | likely_pathogenic | 0.6528 | pathogenic | -1.855 | Destabilizing | 0.937 | D | 0.685 | prob.neutral | N | 0.473349659 | None | None | N |
| C/T | 0.7889 | likely_pathogenic | 0.7748 | pathogenic | -1.427 | Destabilizing | 0.95 | D | 0.689 | prob.neutral | None | None | None | None | N |
| C/V | 0.6329 | likely_pathogenic | 0.6361 | pathogenic | -0.827 | Destabilizing | 0.982 | D | 0.682 | prob.neutral | None | None | None | None | N |
| C/W | 0.9307 | likely_pathogenic | 0.9411 | pathogenic | -1.377 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.529529437 | None | None | N |
| C/Y | 0.8538 | likely_pathogenic | 0.8738 | pathogenic | -1.152 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.475621519 | 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.