Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28147 | 84664;84665;84666 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| N2AB | 26506 | 79741;79742;79743 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| N2A | 25579 | 76960;76961;76962 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| N2B | 19082 | 57469;57470;57471 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| Novex-1 | 19207 | 57844;57845;57846 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| Novex-2 | 19274 | 58045;58046;58047 | chr2:178561693;178561692;178561691 | chr2:179426420;179426419;179426418 |
| 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 | rs1285081649  |
-1.736 | 0.001 | N | 0.345 | 0.256 | 0.572760530292 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| V/A | rs1285081649 |
-1.736 | 0.001 | N | 0.345 | 0.256 | 0.572760530292 | gnomAD-4.0.0 | 2.0612E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.7078E-06 | 0 | 0 |
| V/F | rs1318887192 |
-1.085 | 0.624 | N | 0.801 | 0.292 | 0.807043397782 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs1318887192 |
-1.085 | 0.624 | N | 0.801 | 0.292 | 0.807043397782 | gnomAD-4.0.0 | 1.60743E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78753E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.033 | N | 0.646 | 0.134 | 0.445811967706 | gnomAD-4.0.0 | 1.60743E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89109E-06 | 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 | 0.1571 | likely_benign | 0.1826 | benign | -0.996 | Destabilizing | 0.001 | N | 0.345 | neutral | N | 0.503855809 | None | None | N |
| V/C | 0.6905 | likely_pathogenic | 0.7073 | pathogenic | -0.844 | Destabilizing | 0.944 | D | 0.747 | deleterious | None | None | None | None | N |
| V/D | 0.5265 | ambiguous | 0.5913 | pathogenic | -0.546 | Destabilizing | 0.771 | D | 0.844 | deleterious | N | 0.506137215 | None | None | N |
| V/E | 0.3404 | ambiguous | 0.388 | ambiguous | -0.605 | Destabilizing | 0.687 | D | 0.727 | deleterious | None | None | None | None | N |
| V/F | 0.1682 | likely_benign | 0.1913 | benign | -0.869 | Destabilizing | 0.624 | D | 0.801 | deleterious | N | 0.503855809 | None | None | N |
| V/G | 0.3222 | likely_benign | 0.3794 | ambiguous | -1.231 | Destabilizing | 0.191 | N | 0.798 | deleterious | N | 0.505376746 | None | None | N |
| V/H | 0.5042 | ambiguous | 0.5449 | ambiguous | -0.666 | Destabilizing | 0.981 | D | 0.811 | deleterious | None | None | None | None | N |
| V/I | 0.0685 | likely_benign | 0.072 | benign | -0.492 | Destabilizing | 0.001 | N | 0.404 | neutral | N | 0.484337304 | None | None | N |
| V/K | 0.2054 | likely_benign | 0.2214 | benign | -0.822 | Destabilizing | 0.687 | D | 0.714 | prob.delet. | None | None | None | None | N |
| V/L | 0.1294 | likely_benign | 0.1548 | benign | -0.492 | Destabilizing | 0.033 | N | 0.646 | neutral | N | 0.490628558 | None | None | N |
| V/M | 0.1168 | likely_benign | 0.1291 | benign | -0.439 | Destabilizing | 0.687 | D | 0.689 | prob.delet. | None | None | None | None | N |
| V/N | 0.3401 | ambiguous | 0.3856 | ambiguous | -0.593 | Destabilizing | 0.817 | D | 0.853 | deleterious | None | None | None | None | N |
| V/P | 0.5061 | ambiguous | 0.6258 | pathogenic | -0.624 | Destabilizing | 0.817 | D | 0.8 | deleterious | None | None | None | None | N |
| V/Q | 0.2799 | likely_benign | 0.2976 | benign | -0.808 | Destabilizing | 0.817 | D | 0.779 | deleterious | None | None | None | None | N |
| V/R | 0.1826 | likely_benign | 0.1971 | benign | -0.266 | Destabilizing | 0.817 | D | 0.847 | deleterious | None | None | None | None | N |
| V/S | 0.244 | likely_benign | 0.2821 | benign | -1.092 | Destabilizing | 0.239 | N | 0.777 | deleterious | None | None | None | None | N |
| V/T | 0.1164 | likely_benign | 0.1246 | benign | -1.042 | Destabilizing | 0.008 | N | 0.451 | neutral | None | None | None | None | N |
| V/W | 0.7753 | likely_pathogenic | 0.8137 | pathogenic | -0.958 | Destabilizing | 0.981 | D | 0.789 | deleterious | None | None | None | None | N |
| V/Y | 0.5322 | ambiguous | 0.5562 | ambiguous | -0.678 | Destabilizing | 0.817 | D | 0.767 | 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.