Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22017 | 66274;66275;66276 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| N2AB | 20376 | 61351;61352;61353 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| N2A | 19449 | 58570;58571;58572 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| N2B | 12952 | 39079;39080;39081 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| Novex-1 | 13077 | 39454;39455;39456 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| Novex-2 | 13144 | 39655;39656;39657 | chr2:178582407;178582406;178582405 | chr2:179447134;179447133;179447132 |
| 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/A | None | None | 0.939 | N | 0.639 | 0.391 | 0.507213507908 | gnomAD-4.0.0 | 6.84611E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99831E-07 | 0 | 0 |
| V/M | rs375663566  |
-0.544 | 0.997 | N | 0.713 | 0.462 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 1.294E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| V/M | rs375663566 |
-0.544 | 0.997 | N | 0.713 | 0.462 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs375663566 |
-0.544 | 0.997 | N | 0.713 | 0.462 | None | gnomAD-4.0.0 | 2.04618E-05 | None | None | None | None | N | None | 9.35179E-05 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 1.69586E-05 | 2.19703E-05 | 4.80708E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.572 | likely_pathogenic | 0.5091 | ambiguous | -1.859 | Destabilizing | 0.939 | D | 0.639 | neutral | N | 0.519660599 | None | None | N |
| V/C | 0.948 | likely_pathogenic | 0.9353 | pathogenic | -1.398 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| V/D | 0.9965 | likely_pathogenic | 0.997 | pathogenic | -2.107 | Highly Destabilizing | 0.998 | D | 0.842 | deleterious | None | None | None | None | N |
| V/E | 0.9858 | likely_pathogenic | 0.9862 | pathogenic | -1.903 | Destabilizing | 0.997 | D | 0.833 | deleterious | D | 0.54278289 | None | None | N |
| V/F | 0.7916 | likely_pathogenic | 0.8115 | pathogenic | -1.079 | Destabilizing | 0.986 | D | 0.769 | deleterious | None | None | None | None | N |
| V/G | 0.9338 | likely_pathogenic | 0.9294 | pathogenic | -2.393 | Highly Destabilizing | 0.997 | D | 0.847 | deleterious | D | 0.531262 | None | None | N |
| V/H | 0.9961 | likely_pathogenic | 0.9954 | pathogenic | -2.09 | Highly Destabilizing | 0.999 | D | 0.86 | deleterious | None | None | None | None | N |
| V/I | 0.0898 | likely_benign | 0.0951 | benign | -0.388 | Destabilizing | 0.06 | N | 0.191 | neutral | None | None | None | None | N |
| V/K | 0.9916 | likely_pathogenic | 0.9918 | pathogenic | -1.587 | Destabilizing | 0.993 | D | 0.835 | deleterious | None | None | None | None | N |
| V/L | 0.6496 | likely_pathogenic | 0.6734 | pathogenic | -0.388 | Destabilizing | 0.889 | D | 0.557 | neutral | N | 0.506800371 | None | None | N |
| V/M | 0.5964 | likely_pathogenic | 0.6038 | pathogenic | -0.409 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.512650766 | None | None | N |
| V/N | 0.987 | likely_pathogenic | 0.9866 | pathogenic | -1.826 | Destabilizing | 0.998 | D | 0.877 | deleterious | None | None | None | None | N |
| V/P | 0.9838 | likely_pathogenic | 0.9826 | pathogenic | -0.848 | Destabilizing | 0.998 | D | 0.838 | deleterious | None | None | None | None | N |
| V/Q | 0.984 | likely_pathogenic | 0.9819 | pathogenic | -1.676 | Destabilizing | 0.998 | D | 0.874 | deleterious | None | None | None | None | N |
| V/R | 0.9858 | likely_pathogenic | 0.9851 | pathogenic | -1.438 | Destabilizing | 0.998 | D | 0.882 | deleterious | None | None | None | None | N |
| V/S | 0.9143 | likely_pathogenic | 0.8886 | pathogenic | -2.485 | Highly Destabilizing | 0.993 | D | 0.832 | deleterious | None | None | None | None | N |
| V/T | 0.7129 | likely_pathogenic | 0.6483 | pathogenic | -2.125 | Highly Destabilizing | 0.953 | D | 0.671 | neutral | None | None | None | None | N |
| V/W | 0.9966 | likely_pathogenic | 0.9965 | pathogenic | -1.542 | Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| V/Y | 0.9877 | likely_pathogenic | 0.9873 | pathogenic | -1.134 | Destabilizing | 0.998 | D | 0.771 | 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.