Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3226 | 9901;9902;9903 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| N2AB | 3226 | 9901;9902;9903 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| N2A | 3226 | 9901;9902;9903 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| N2B | 3180 | 9763;9764;9765 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| Novex-1 | 3180 | 9763;9764;9765 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| Novex-2 | 3180 | 9763;9764;9765 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
| Novex-3 | 3226 | 9901;9902;9903 | chr2:178766408;178766407;178766406 | chr2:179631135;179631134;179631133 |
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/K | rs769991631  |
-0.454 | 0.997 | N | 0.591 | 0.232 | 0.187945064343 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.93E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs769991631 |
-0.454 | 0.997 | N | 0.591 | 0.232 | 0.187945064343 | gnomAD-4.0.0 | 1.59061E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.7669E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 1.0 | N | 0.779 | 0.222 | 0.154104182512 | gnomAD-4.0.0 | 1.20063E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31284E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8927 | likely_pathogenic | 0.8563 | pathogenic | -0.245 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/C | 0.6124 | likely_pathogenic | 0.5207 | ambiguous | -0.358 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/D | 0.9752 | likely_pathogenic | 0.959 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| R/E | 0.7983 | likely_pathogenic | 0.7539 | pathogenic | 0.049 | Stabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/F | 0.905 | likely_pathogenic | 0.897 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/G | 0.8771 | likely_pathogenic | 0.8358 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.384455659 | None | None | N |
| R/H | 0.2785 | likely_benign | 0.2465 | benign | -0.835 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| R/I | 0.6735 | likely_pathogenic | 0.6447 | pathogenic | 0.223 | Stabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/K | 0.266 | likely_benign | 0.2575 | benign | -0.235 | Destabilizing | 0.997 | D | 0.591 | neutral | N | 0.328726009 | None | None | N |
| R/L | 0.6972 | likely_pathogenic | 0.6782 | pathogenic | 0.223 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/M | 0.7721 | likely_pathogenic | 0.7556 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.332016108 | None | None | N |
| R/N | 0.933 | likely_pathogenic | 0.9056 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/P | 0.9882 | likely_pathogenic | 0.9814 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/Q | 0.2614 | likely_benign | 0.2462 | benign | -0.104 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/S | 0.8978 | likely_pathogenic | 0.8556 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.33347729 | None | None | N |
| R/T | 0.7305 | likely_pathogenic | 0.6585 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.335252908 | None | None | N |
| R/V | 0.7587 | likely_pathogenic | 0.7129 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/W | 0.5724 | likely_pathogenic | 0.5734 | pathogenic | -0.476 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.385233455 | None | None | N |
| R/Y | 0.799 | likely_pathogenic | 0.7732 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.77 | 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.