Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20952 | 63079;63080;63081 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| N2AB | 19311 | 58156;58157;58158 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| N2A | 18384 | 55375;55376;55377 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| N2B | 11887 | 35884;35885;35886 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| Novex-1 | 12012 | 36259;36260;36261 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| Novex-2 | 12079 | 36460;36461;36462 | chr2:178588871;178588870;178588869 | chr2:179453598;179453597;179453596 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs769683530  |
-1.127 | 0.115 | N | 0.525 | 0.287 | 0.257786959452 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs769683530 |
-1.127 | 0.115 | N | 0.525 | 0.287 | 0.257786959452 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/R | rs748109390 |
-0.39 | 0.314 | D | 0.683 | 0.436 | 0.259761712551 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs748109390 |
-0.39 | 0.314 | D | 0.683 | 0.436 | 0.259761712551 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs748109390 |
-0.39 | 0.314 | D | 0.683 | 0.436 | 0.259761712551 | gnomAD-4.0.0 | 6.58033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47137E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2953 | likely_benign | 0.3613 | ambiguous | -0.414 | Destabilizing | 0.034 | N | 0.451 | neutral | None | None | None | None | N |
| S/C | 0.3405 | ambiguous | 0.3841 | ambiguous | -0.246 | Destabilizing | 0.778 | D | 0.696 | prob.delet. | N | 0.510844022 | None | None | N |
| S/D | 0.9612 | likely_pathogenic | 0.9503 | pathogenic | -0.058 | Destabilizing | 0.147 | N | 0.587 | neutral | None | None | None | None | N |
| S/E | 0.9868 | likely_pathogenic | 0.9826 | pathogenic | 0.046 | Stabilizing | 0.147 | N | 0.579 | neutral | None | None | None | None | N |
| S/F | 0.9539 | likely_pathogenic | 0.9495 | pathogenic | -0.337 | Destabilizing | 0.552 | D | 0.777 | deleterious | None | None | None | None | N |
| S/G | 0.244 | likely_benign | 0.2704 | benign | -0.755 | Destabilizing | 0.115 | N | 0.525 | neutral | N | 0.487370942 | None | None | N |
| S/H | 0.9737 | likely_pathogenic | 0.9694 | pathogenic | -1.106 | Destabilizing | 0.934 | D | 0.695 | prob.delet. | None | None | None | None | N |
| S/I | 0.8658 | likely_pathogenic | 0.8691 | pathogenic | 0.411 | Stabilizing | 0.186 | N | 0.67 | prob.neutral | N | 0.496258486 | None | None | N |
| S/K | 0.9969 | likely_pathogenic | 0.9956 | pathogenic | -0.165 | Destabilizing | 0.147 | N | 0.589 | neutral | None | None | None | None | N |
| S/L | 0.5917 | likely_pathogenic | 0.626 | pathogenic | 0.411 | Stabilizing | 0.08 | N | 0.685 | prob.delet. | None | None | None | None | N |
| S/M | 0.5953 | likely_pathogenic | 0.6246 | pathogenic | 0.239 | Stabilizing | 0.823 | D | 0.694 | prob.delet. | None | None | None | None | N |
| S/N | 0.8032 | likely_pathogenic | 0.7807 | pathogenic | -0.446 | Destabilizing | 0.115 | N | 0.618 | neutral | N | 0.494714776 | None | None | N |
| S/P | 0.9883 | likely_pathogenic | 0.9888 | pathogenic | 0.173 | Stabilizing | 0.552 | D | 0.684 | prob.delet. | None | None | None | None | N |
| S/Q | 0.9826 | likely_pathogenic | 0.9793 | pathogenic | -0.328 | Destabilizing | 0.552 | D | 0.634 | neutral | None | None | None | None | N |
| S/R | 0.9964 | likely_pathogenic | 0.9955 | pathogenic | -0.389 | Destabilizing | 0.314 | N | 0.683 | prob.neutral | D | 0.528694787 | None | None | N |
| S/T | 0.0698 | likely_benign | 0.0867 | benign | -0.322 | Destabilizing | None | N | 0.179 | neutral | N | 0.474179025 | None | None | N |
| S/V | 0.7383 | likely_pathogenic | 0.7671 | pathogenic | 0.173 | Stabilizing | 0.08 | N | 0.691 | prob.delet. | None | None | None | None | N |
| S/W | 0.9745 | likely_pathogenic | 0.9681 | pathogenic | -0.482 | Destabilizing | 0.934 | D | 0.865 | deleterious | None | None | None | None | N |
| S/Y | 0.95 | likely_pathogenic | 0.9392 | pathogenic | -0.076 | Destabilizing | 0.552 | D | 0.775 | 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.