Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22029 | 66310;66311;66312 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| N2AB | 20388 | 61387;61388;61389 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| N2A | 19461 | 58606;58607;58608 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| N2B | 12964 | 39115;39116;39117 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| Novex-1 | 13089 | 39490;39491;39492 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| Novex-2 | 13156 | 39691;39692;39693 | chr2:178582371;178582370;178582369 | chr2:179447098;179447097;179447096 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs769739080  |
-1.766 | 1.0 | D | 0.813 | 0.576 | 0.766150250677 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 2.85E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/C | rs769739080 |
-1.766 | 1.0 | D | 0.813 | 0.576 | 0.766150250677 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07641E-04 | 0 |
| R/C | rs769739080 |
-1.766 | 1.0 | D | 0.813 | 0.576 | 0.766150250677 | gnomAD-4.0.0 | 8.06415E-06 | None | None | None | None | N | None | 0 | 1.67163E-05 | None | 0 | 0 | None | 0 | 1.64853E-04 | 6.78464E-06 | 3.30222E-05 | 0 |
| R/H | rs72646868 |
-2.349 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-2.1.1 | 5.02E-05 | None | None | None | None | N | None | 0 | 5.7E-05 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 8.63E-05 | 0 |
| R/H | rs72646868 |
-2.349 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-3.1.2 | 7.9E-05 | None | None | None | None | N | None | 2.42E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47132E-04 | 0 | 0 |
| R/H | rs72646868 |
-2.349 | 1.0 | D | 0.813 | 0.572 | None | gnomAD-4.0.0 | 7.69259E-05 | None | None | None | None | N | None | 8.02203E-05 | 5.01572E-05 | None | 0 | 6.71532E-05 | None | 0 | 1.64853E-04 | 9.07487E-05 | 1.10154E-05 | 4.81047E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9949 | likely_pathogenic | 0.9841 | pathogenic | -2.056 | Highly Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| R/C | 0.8442 | likely_pathogenic | 0.6355 | pathogenic | -1.94 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.537120896 | None | None | N |
| R/D | 0.9992 | likely_pathogenic | 0.9982 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/E | 0.9883 | likely_pathogenic | 0.9717 | pathogenic | -1.2 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| R/F | 0.9964 | likely_pathogenic | 0.9891 | pathogenic | -1.077 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| R/G | 0.992 | likely_pathogenic | 0.9766 | pathogenic | -2.418 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.543450772 | None | None | N |
| R/H | 0.7065 | likely_pathogenic | 0.4734 | ambiguous | -1.915 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.555225151 | None | None | N |
| R/I | 0.9847 | likely_pathogenic | 0.9584 | pathogenic | -0.984 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| R/K | 0.7019 | likely_pathogenic | 0.5681 | pathogenic | -1.168 | Destabilizing | 0.998 | D | 0.666 | neutral | None | None | None | None | N |
| R/L | 0.9711 | likely_pathogenic | 0.9335 | pathogenic | -0.984 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.543704261 | None | None | N |
| R/M | 0.9883 | likely_pathogenic | 0.963 | pathogenic | -1.474 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/N | 0.9962 | likely_pathogenic | 0.9906 | pathogenic | -1.643 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/P | 0.9998 | likely_pathogenic | 0.9994 | pathogenic | -1.333 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.55547864 | None | None | N |
| R/Q | 0.683 | likely_pathogenic | 0.4725 | ambiguous | -1.393 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| R/S | 0.9947 | likely_pathogenic | 0.984 | pathogenic | -2.433 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.528799103 | None | None | N |
| R/T | 0.9943 | likely_pathogenic | 0.9821 | pathogenic | -1.966 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/V | 0.9886 | likely_pathogenic | 0.968 | pathogenic | -1.333 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/W | 0.9362 | likely_pathogenic | 0.8432 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/Y | 0.9855 | likely_pathogenic | 0.9601 | pathogenic | -0.54 | Destabilizing | 1.0 | D | 0.836 | 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.