Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21751 | 65476;65477;65478 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| N2AB | 20110 | 60553;60554;60555 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| N2A | 19183 | 57772;57773;57774 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| N2B | 12686 | 38281;38282;38283 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| Novex-1 | 12811 | 38656;38657;38658 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| Novex-2 | 12878 | 38857;38858;38859 | chr2:178584300;178584299;178584298 | chr2:179449027;179449026;179449025 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | rs770569025  |
-0.461 | 0.001 | N | 0.145 | 0.105 | 0.211220785272 | gnomAD-2.1.1 | 1.72E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.78E-05 | 0 |
| Y/F | rs770569025 |
-0.461 | 0.001 | N | 0.145 | 0.105 | 0.211220785272 | gnomAD-4.0.0 | 3.97688E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.11289E-05 | 0 | 1.69515E-05 |
| Y/H | rs775750677 |
-0.13 | 0.976 | N | 0.634 | 0.185 | 0.29385284311 | gnomAD-2.1.1 | 1.28E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.82E-05 | 0 |
| Y/H | rs775750677 |
-0.13 | 0.976 | N | 0.634 | 0.185 | 0.29385284311 | gnomAD-4.0.0 | 8.2971E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.49475E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4326 | ambiguous | 0.3581 | ambiguous | -2.196 | Highly Destabilizing | 0.505 | D | 0.587 | neutral | None | None | None | None | N |
| Y/C | 0.1988 | likely_benign | 0.1455 | benign | -0.729 | Destabilizing | 0.993 | D | 0.597 | neutral | N | 0.377486692 | None | None | N |
| Y/D | 0.3972 | ambiguous | 0.2931 | benign | -0.423 | Destabilizing | 0.976 | D | 0.655 | prob.neutral | N | 0.44122874 | None | None | N |
| Y/E | 0.7507 | likely_pathogenic | 0.6521 | pathogenic | -0.373 | Destabilizing | 0.982 | D | 0.672 | prob.neutral | None | None | None | None | N |
| Y/F | 0.1057 | likely_benign | 0.0931 | benign | -1.09 | Destabilizing | 0.001 | N | 0.145 | neutral | N | 0.387295467 | None | None | N |
| Y/G | 0.4331 | ambiguous | 0.3548 | ambiguous | -2.482 | Highly Destabilizing | 0.834 | D | 0.681 | prob.neutral | None | None | None | None | N |
| Y/H | 0.3608 | ambiguous | 0.268 | benign | -0.855 | Destabilizing | 0.976 | D | 0.634 | neutral | N | 0.422200262 | None | None | N |
| Y/I | 0.579 | likely_pathogenic | 0.4736 | ambiguous | -1.353 | Destabilizing | 0.008 | N | 0.275 | neutral | None | None | None | None | N |
| Y/K | 0.798 | likely_pathogenic | 0.7293 | pathogenic | -0.804 | Destabilizing | 0.946 | D | 0.677 | prob.neutral | None | None | None | None | N |
| Y/L | 0.5031 | ambiguous | 0.4461 | ambiguous | -1.353 | Destabilizing | 0.003 | N | 0.25 | neutral | None | None | None | None | N |
| Y/M | 0.6028 | likely_pathogenic | 0.5494 | ambiguous | -0.921 | Destabilizing | 0.897 | D | 0.693 | prob.delet. | None | None | None | None | N |
| Y/N | 0.2372 | likely_benign | 0.1757 | benign | -0.932 | Destabilizing | 0.976 | D | 0.669 | prob.neutral | N | 0.430011668 | None | None | N |
| Y/P | 0.4499 | ambiguous | 0.3906 | ambiguous | -1.626 | Destabilizing | 0.982 | D | 0.631 | neutral | None | None | None | None | N |
| Y/Q | 0.7327 | likely_pathogenic | 0.6131 | pathogenic | -0.972 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | None | None | None | None | N |
| Y/R | 0.7342 | likely_pathogenic | 0.641 | pathogenic | -0.263 | Destabilizing | 0.982 | D | 0.668 | prob.neutral | None | None | None | None | N |
| Y/S | 0.3057 | likely_benign | 0.2297 | benign | -1.554 | Destabilizing | 0.791 | D | 0.663 | prob.neutral | N | 0.410905833 | None | None | N |
| Y/T | 0.5112 | ambiguous | 0.4039 | ambiguous | -1.415 | Destabilizing | 0.712 | D | 0.655 | prob.neutral | None | None | None | None | N |
| Y/V | 0.456 | ambiguous | 0.3746 | ambiguous | -1.626 | Destabilizing | 0.338 | N | 0.516 | neutral | None | None | None | None | N |
| Y/W | 0.4948 | ambiguous | 0.4223 | ambiguous | -0.698 | Destabilizing | 0.982 | D | 0.629 | neutral | 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.