Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26401 | 79426;79427;79428 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| N2AB | 24760 | 74503;74504;74505 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| N2A | 23833 | 71722;71723;71724 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| N2B | 17336 | 52231;52232;52233 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| Novex-1 | 17461 | 52606;52607;52608 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| Novex-2 | 17528 | 52807;52808;52809 | chr2:178566931;178566930;178566929 | chr2:179431658;179431657;179431656 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 0.988 | N | 0.655 | 0.331 | 0.227260227426 | gnomAD-4.0.0 | 6.84274E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99538E-07 | 0 | 0 |
| D/Y | rs1427205421  |
-0.492 | 0.999 | N | 0.692 | 0.426 | 0.65374614097 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/Y | rs1427205421 |
-0.492 | 0.999 | N | 0.692 | 0.426 | 0.65374614097 | gnomAD-4.0.0 | 1.36855E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79908E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7063 | likely_pathogenic | 0.7163 | pathogenic | -0.473 | Destabilizing | 0.988 | D | 0.687 | prob.neutral | N | 0.498324584 | None | None | N |
| D/C | 0.9412 | likely_pathogenic | 0.943 | pathogenic | 0.165 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/E | 0.347 | ambiguous | 0.3769 | ambiguous | -0.526 | Destabilizing | 0.067 | N | 0.315 | neutral | N | 0.52073246 | None | None | N |
| D/F | 0.9143 | likely_pathogenic | 0.9106 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/G | 0.5291 | ambiguous | 0.5448 | ambiguous | -0.674 | Destabilizing | 0.958 | D | 0.68 | prob.neutral | N | 0.520905818 | None | None | N |
| D/H | 0.8093 | likely_pathogenic | 0.8137 | pathogenic | -0.875 | Destabilizing | 0.998 | D | 0.669 | neutral | N | 0.472320291 | None | None | N |
| D/I | 0.891 | likely_pathogenic | 0.8907 | pathogenic | 0.013 | Stabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/K | 0.9141 | likely_pathogenic | 0.92 | pathogenic | 0.266 | Stabilizing | 0.982 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/L | 0.8767 | likely_pathogenic | 0.8814 | pathogenic | 0.013 | Stabilizing | 0.991 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/M | 0.9372 | likely_pathogenic | 0.9359 | pathogenic | 0.449 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| D/N | 0.2651 | likely_benign | 0.2595 | benign | 0.034 | Stabilizing | 0.988 | D | 0.655 | neutral | N | 0.465588466 | None | None | N |
| D/P | 0.9918 | likely_pathogenic | 0.9915 | pathogenic | -0.128 | Destabilizing | 0.995 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Q | 0.841 | likely_pathogenic | 0.8507 | pathogenic | 0.023 | Stabilizing | 0.982 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/R | 0.9283 | likely_pathogenic | 0.9309 | pathogenic | 0.193 | Stabilizing | 0.991 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/S | 0.509 | ambiguous | 0.5141 | ambiguous | -0.092 | Destabilizing | 0.968 | D | 0.625 | neutral | None | None | None | None | N |
| D/T | 0.6651 | likely_pathogenic | 0.6859 | pathogenic | 0.067 | Stabilizing | 0.991 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/V | 0.7548 | likely_pathogenic | 0.7604 | pathogenic | -0.128 | Destabilizing | 0.994 | D | 0.713 | prob.delet. | N | 0.516682329 | None | None | N |
| D/W | 0.9848 | likely_pathogenic | 0.9854 | pathogenic | -0.621 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/Y | 0.6251 | likely_pathogenic | 0.6193 | pathogenic | -0.465 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | N | 0.511655899 | 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.