Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1711 | 5356;5357;5358 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| N2AB | 1711 | 5356;5357;5358 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| N2A | 1711 | 5356;5357;5358 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| N2B | 1665 | 5218;5219;5220 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| Novex-1 | 1665 | 5218;5219;5220 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| Novex-2 | 1665 | 5218;5219;5220 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
| Novex-3 | 1711 | 5356;5357;5358 | chr2:178776733;178776732;178776731 | chr2:179641460;179641459;179641458 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs397517641  |
-1.011 | 1.0 | D | 0.816 | 0.676 | 0.845695947675 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.78009E-04 |
| S/F | rs397517641 |
-1.011 | 1.0 | D | 0.816 | 0.676 | 0.845695947675 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 3.92516E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| S/F | rs397517641 |
-1.011 | 1.0 | D | 0.816 | 0.676 | 0.845695947675 | gnomAD-4.0.0 | 1.05323E-05 | None | None | None | None | N | None | 1.33273E-05 | 1.16647E-04 | None | 0 | 0 | None | 0 | 0 | 8.47449E-07 | 0 | 1.27988E-04 |
| S/P | None | None | 1.0 | N | 0.812 | 0.68 | 0.450055297382 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2498 | likely_benign | 0.2414 | benign | -0.314 | Destabilizing | 0.997 | D | 0.429 | neutral | N | 0.515252094 | None | None | N |
| S/C | 0.5995 | likely_pathogenic | 0.5891 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.686618843 | None | None | N |
| S/D | 0.9033 | likely_pathogenic | 0.8844 | pathogenic | 0.348 | Stabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| S/E | 0.9619 | likely_pathogenic | 0.9549 | pathogenic | 0.264 | Stabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| S/F | 0.8956 | likely_pathogenic | 0.8899 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.816 | deleterious | D | 0.685767017 | None | None | N |
| S/G | 0.278 | likely_benign | 0.2873 | benign | -0.42 | Destabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | N |
| S/H | 0.8514 | likely_pathogenic | 0.8542 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| S/I | 0.8586 | likely_pathogenic | 0.8685 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| S/K | 0.9901 | likely_pathogenic | 0.9897 | pathogenic | -0.326 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| S/L | 0.6345 | likely_pathogenic | 0.6731 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/M | 0.7763 | likely_pathogenic | 0.8006 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| S/N | 0.4621 | ambiguous | 0.4769 | ambiguous | -0.138 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| S/P | 0.4372 | ambiguous | 0.6093 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.812 | deleterious | N | 0.516119685 | None | None | N |
| S/Q | 0.9302 | likely_pathogenic | 0.9324 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| S/R | 0.9856 | likely_pathogenic | 0.9835 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| S/T | 0.2678 | likely_benign | 0.2757 | benign | -0.226 | Destabilizing | 0.999 | D | 0.475 | neutral | D | 0.561928935 | None | None | N |
| S/V | 0.7734 | likely_pathogenic | 0.7848 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| S/W | 0.9406 | likely_pathogenic | 0.9367 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| S/Y | 0.8296 | likely_pathogenic | 0.8257 | pathogenic | -0.679 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.647281155 | 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.