Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31680 | 95263;95264;95265 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| N2AB | 30039 | 90340;90341;90342 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| N2A | 29112 | 87559;87560;87561 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| N2B | 22615 | 68068;68069;68070 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| Novex-1 | 22740 | 68443;68444;68445 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| Novex-2 | 22807 | 68644;68645;68646 | chr2:178546293;178546292;178546291 | chr2:179411020;179411019;179411018 |
| 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/G | rs760992930  |
-0.377 | 1.0 | N | 0.586 | 0.426 | 0.424194796918 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/G | rs760992930 |
-0.377 | 1.0 | N | 0.586 | 0.426 | 0.424194796918 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85838E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9611 | likely_pathogenic | 0.9741 | pathogenic | -0.02 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | N |
| R/C | 0.7644 | likely_pathogenic | 0.8151 | pathogenic | -0.204 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/D | 0.99 | likely_pathogenic | 0.9925 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/E | 0.943 | likely_pathogenic | 0.9584 | pathogenic | -0.168 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| R/F | 0.9833 | likely_pathogenic | 0.9883 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/G | 0.9445 | likely_pathogenic | 0.9626 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.586 | neutral | N | 0.509550807 | None | None | N |
| R/H | 0.6224 | likely_pathogenic | 0.6762 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/I | 0.8845 | likely_pathogenic | 0.9152 | pathogenic | 0.325 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.481785313 | None | None | N |
| R/K | 0.4819 | ambiguous | 0.5622 | ambiguous | -0.137 | Destabilizing | 0.997 | D | 0.517 | neutral | N | 0.51115768 | None | None | N |
| R/L | 0.8601 | likely_pathogenic | 0.8878 | pathogenic | 0.325 | Stabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | N |
| R/M | 0.9436 | likely_pathogenic | 0.9622 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/N | 0.9794 | likely_pathogenic | 0.9859 | pathogenic | 0.038 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/P | 0.9689 | likely_pathogenic | 0.9748 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/Q | 0.556 | ambiguous | 0.6312 | pathogenic | -0.052 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/S | 0.9788 | likely_pathogenic | 0.9864 | pathogenic | -0.228 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.457426861 | None | None | N |
| R/T | 0.9417 | likely_pathogenic | 0.9645 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.459895623 | None | None | N |
| R/V | 0.9294 | likely_pathogenic | 0.9508 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/W | 0.8447 | likely_pathogenic | 0.8619 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| R/Y | 0.9544 | likely_pathogenic | 0.9642 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.