Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2776 | 8551;8552;8553 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| N2AB | 2776 | 8551;8552;8553 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| N2A | 2776 | 8551;8552;8553 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| N2B | 2730 | 8413;8414;8415 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| Novex-1 | 2730 | 8413;8414;8415 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| Novex-2 | 2730 | 8413;8414;8415 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
| Novex-3 | 2776 | 8551;8552;8553 | chr2:178770466;178770465;178770464 | chr2:179635193;179635192;179635191 |
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/F | rs752456093  |
-0.685 | 1.0 | D | 0.806 | 0.488 | 0.870576066431 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs752456093 |
-0.685 | 1.0 | D | 0.806 | 0.488 | 0.870576066431 | gnomAD-4.0.0 | 1.59052E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77423E-05 | 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 | 0.4379 | ambiguous | 0.4858 | ambiguous | -0.597 | Destabilizing | 0.999 | D | 0.627 | neutral | D | 0.539184951 | None | None | I |
| V/C | 0.9221 | likely_pathogenic | 0.9373 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| V/D | 0.7925 | likely_pathogenic | 0.8421 | pathogenic | 0.011 | Stabilizing | 1.0 | D | 0.83 | deleterious | N | 0.505109155 | None | None | I |
| V/E | 0.6828 | likely_pathogenic | 0.7628 | pathogenic | -0.057 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| V/F | 0.4048 | ambiguous | 0.4308 | ambiguous | -0.601 | Destabilizing | 1.0 | D | 0.806 | deleterious | D | 0.568247835 | None | None | I |
| V/G | 0.5633 | ambiguous | 0.6313 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.542892101 | None | None | I |
| V/H | 0.8824 | likely_pathogenic | 0.9005 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| V/I | 0.0971 | likely_benign | 0.0964 | benign | -0.284 | Destabilizing | 0.997 | D | 0.522 | neutral | D | 0.539919334 | None | None | I |
| V/K | 0.8254 | likely_pathogenic | 0.8632 | pathogenic | -0.424 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| V/L | 0.3917 | ambiguous | 0.4034 | ambiguous | -0.284 | Destabilizing | 0.997 | D | 0.587 | neutral | D | 0.541720874 | None | None | I |
| V/M | 0.2741 | likely_benign | 0.296 | benign | -0.513 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| V/N | 0.5317 | ambiguous | 0.5836 | pathogenic | -0.282 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| V/P | 0.8794 | likely_pathogenic | 0.9013 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| V/Q | 0.7026 | likely_pathogenic | 0.753 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| V/R | 0.7757 | likely_pathogenic | 0.8005 | pathogenic | 0.03 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| V/S | 0.4511 | ambiguous | 0.5104 | ambiguous | -0.742 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| V/T | 0.3716 | ambiguous | 0.4277 | ambiguous | -0.694 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| V/W | 0.964 | likely_pathogenic | 0.9715 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| V/Y | 0.8345 | likely_pathogenic | 0.8584 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
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.