Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26840 | 80743;80744;80745 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| N2AB | 25199 | 75820;75821;75822 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| N2A | 24272 | 73039;73040;73041 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| N2B | 17775 | 53548;53549;53550 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| Novex-1 | 17900 | 53923;53924;53925 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| Novex-2 | 17967 | 54124;54125;54126 | chr2:178565614;178565613;178565612 | chr2:179430341;179430340;179430339 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.781 | D | 0.823 | 0.554 | 0.742137632746 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs373144782  |
-0.364 | 0.002 | N | 0.207 | 0.059 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs373144782 |
-0.364 | 0.002 | N | 0.207 | 0.059 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs373144782 |
-0.364 | 0.002 | N | 0.207 | 0.059 | None | gnomAD-4.0.0 | 3.84438E-06 | None | None | None | None | N | None | 5.07734E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6092 | likely_pathogenic | 0.5914 | pathogenic | -1.684 | Destabilizing | 0.334 | N | 0.644 | neutral | N | 0.47553043 | None | None | N |
| V/C | 0.8988 | likely_pathogenic | 0.8928 | pathogenic | -1.438 | Destabilizing | 0.982 | D | 0.777 | deleterious | None | None | None | None | N |
| V/D | 0.9891 | likely_pathogenic | 0.9876 | pathogenic | -1.164 | Destabilizing | 0.781 | D | 0.825 | deleterious | N | 0.501534724 | None | None | N |
| V/E | 0.9658 | likely_pathogenic | 0.9636 | pathogenic | -1.013 | Destabilizing | 0.826 | D | 0.807 | deleterious | None | None | None | None | N |
| V/F | 0.5147 | ambiguous | 0.4162 | ambiguous | -1.038 | Destabilizing | 0.638 | D | 0.771 | deleterious | N | 0.500467859 | None | None | N |
| V/G | 0.8471 | likely_pathogenic | 0.8324 | pathogenic | -2.155 | Highly Destabilizing | 0.781 | D | 0.823 | deleterious | D | 0.538503702 | None | None | N |
| V/H | 0.9834 | likely_pathogenic | 0.9774 | pathogenic | -1.663 | Destabilizing | 0.982 | D | 0.833 | deleterious | None | None | None | None | N |
| V/I | 0.0773 | likely_benign | 0.0709 | benign | -0.422 | Destabilizing | 0.002 | N | 0.207 | neutral | N | 0.479291269 | None | None | N |
| V/K | 0.9723 | likely_pathogenic | 0.9687 | pathogenic | -1.26 | Destabilizing | 0.826 | D | 0.811 | deleterious | None | None | None | None | N |
| V/L | 0.4085 | ambiguous | 0.3577 | ambiguous | -0.422 | Destabilizing | 0.034 | N | 0.585 | neutral | N | 0.463433596 | None | None | N |
| V/M | 0.461 | ambiguous | 0.3927 | ambiguous | -0.575 | Destabilizing | 0.7 | D | 0.721 | prob.delet. | None | None | None | None | N |
| V/N | 0.9665 | likely_pathogenic | 0.9607 | pathogenic | -1.361 | Destabilizing | 0.935 | D | 0.861 | deleterious | None | None | None | None | N |
| V/P | 0.9658 | likely_pathogenic | 0.9661 | pathogenic | -0.81 | Destabilizing | 0.935 | D | 0.81 | deleterious | None | None | None | None | N |
| V/Q | 0.9609 | likely_pathogenic | 0.9565 | pathogenic | -1.256 | Destabilizing | 0.935 | D | 0.85 | deleterious | None | None | None | None | N |
| V/R | 0.9575 | likely_pathogenic | 0.9522 | pathogenic | -1.093 | Destabilizing | 0.826 | D | 0.865 | deleterious | None | None | None | None | N |
| V/S | 0.8858 | likely_pathogenic | 0.871 | pathogenic | -2.096 | Highly Destabilizing | 0.826 | D | 0.805 | deleterious | None | None | None | None | N |
| V/T | 0.7956 | likely_pathogenic | 0.764 | pathogenic | -1.782 | Destabilizing | 0.399 | N | 0.698 | prob.neutral | None | None | None | None | N |
| V/W | 0.982 | likely_pathogenic | 0.9719 | pathogenic | -1.293 | Destabilizing | 0.982 | D | 0.819 | deleterious | None | None | None | None | N |
| V/Y | 0.9287 | likely_pathogenic | 0.9038 | pathogenic | -0.945 | Destabilizing | 0.826 | D | 0.774 | 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.