Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20939 | 63040;63041;63042 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| N2AB | 19298 | 58117;58118;58119 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| N2A | 18371 | 55336;55337;55338 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| N2B | 11874 | 35845;35846;35847 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| Novex-1 | 11999 | 36220;36221;36222 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| Novex-2 | 12066 | 36421;36422;36423 | chr2:178588910;178588909;178588908 | chr2:179453637;179453636;179453635 |
| 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 | rs369694001  |
-1.607 | 1.0 | N | 0.823 | 0.391 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/C | rs369694001 |
-1.607 | 1.0 | N | 0.823 | 0.391 | None | gnomAD-4.0.0 | 8.89892E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16957E-05 | 0 | 0 |
| R/G | rs369694001 |
None | 1.0 | N | 0.774 | 0.434 | 0.442466506703 | 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 |
| R/G | rs369694001 |
None | 1.0 | N | 0.774 | 0.434 | 0.442466506703 | gnomAD-4.0.0 | 1.24009E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69568E-06 | 0 | 0 |
| R/H | rs777095470 |
-2.004 | 1.0 | N | 0.856 | 0.467 | 0.440498838766 | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 4.14E-05 | 2.84E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.13E-05 | 0 |
| R/H | rs777095470 |
-2.004 | 1.0 | N | 0.856 | 0.467 | 0.440498838766 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs777095470 |
-2.004 | 1.0 | N | 0.856 | 0.467 | 0.440498838766 | gnomAD-4.0.0 | 2.41813E-05 | None | None | None | None | N | None | 2.67187E-05 | 1.66995E-05 | None | 0 | 0 | None | 1.56499E-05 | 0 | 2.79786E-05 | 1.0981E-05 | 1.60215E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8712 | likely_pathogenic | 0.8751 | pathogenic | -1.419 | Destabilizing | 0.999 | D | 0.662 | neutral | None | None | None | None | N |
| R/C | 0.3301 | likely_benign | 0.3333 | benign | -1.558 | Destabilizing | 1.0 | D | 0.823 | deleterious | N | 0.474232848 | None | None | N |
| R/D | 0.9873 | likely_pathogenic | 0.9871 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/E | 0.899 | likely_pathogenic | 0.8975 | pathogenic | -0.53 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| R/F | 0.8939 | likely_pathogenic | 0.8905 | pathogenic | -0.997 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| R/G | 0.8446 | likely_pathogenic | 0.8458 | pathogenic | -1.744 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.499325316 | None | None | N |
| R/H | 0.3204 | likely_benign | 0.3079 | benign | -1.717 | Destabilizing | 1.0 | D | 0.856 | deleterious | N | 0.493627323 | None | None | N |
| R/I | 0.8138 | likely_pathogenic | 0.8241 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| R/K | 0.3021 | likely_benign | 0.2993 | benign | -1.42 | Destabilizing | 0.998 | D | 0.638 | neutral | None | None | None | None | N |
| R/L | 0.7284 | likely_pathogenic | 0.7501 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.478143187 | None | None | N |
| R/M | 0.6887 | likely_pathogenic | 0.6876 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| R/N | 0.9575 | likely_pathogenic | 0.9547 | pathogenic | -1.045 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| R/P | 0.9978 | likely_pathogenic | 0.9981 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.811 | deleterious | N | 0.506162171 | None | None | N |
| R/Q | 0.2762 | likely_benign | 0.2718 | benign | -1.089 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| R/S | 0.8764 | likely_pathogenic | 0.8595 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.768 | deleterious | N | 0.479155196 | None | None | N |
| R/T | 0.7429 | likely_pathogenic | 0.8056 | pathogenic | -1.516 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/V | 0.8113 | likely_pathogenic | 0.8385 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/W | 0.5343 | ambiguous | 0.54 | ambiguous | -0.576 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/Y | 0.7991 | likely_pathogenic | 0.8025 | pathogenic | -0.316 | Destabilizing | 1.0 | D | 0.839 | 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.