Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27874 | 83845;83846;83847 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| N2AB | 26233 | 78922;78923;78924 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| N2A | 25306 | 76141;76142;76143 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| N2B | 18809 | 56650;56651;56652 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| Novex-1 | 18934 | 57025;57026;57027 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| Novex-2 | 19001 | 57226;57227;57228 | chr2:178562512;178562511;178562510 | chr2:179427239;179427238;179427237 |
| 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/E | rs771240950  |
0.042 | 0.994 | N | 0.393 | 0.214 | 0.168933306366 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/E | rs771240950 |
0.042 | 0.994 | N | 0.393 | 0.214 | 0.168933306366 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs771240950 |
0.042 | 0.994 | N | 0.393 | 0.214 | 0.168933306366 | gnomAD-4.0.0 | 6.82346E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32686E-06 | 0 | 0 |
| D/G | rs1377067134 |
None | 1.0 | N | 0.717 | 0.613 | 0.297031009988 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs1377067134 |
None | 1.0 | N | 0.717 | 0.613 | 0.297031009988 | gnomAD-4.0.0 | 5.07499E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.02468E-06 | 0 | 0 |
| D/V | rs1377067134 |
0.344 | 1.0 | N | 0.743 | 0.614 | 0.692570320384 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 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 | 0.7173 | likely_pathogenic | 0.7073 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.479255596 | None | None | N |
| D/C | 0.9718 | likely_pathogenic | 0.9725 | pathogenic | -0.139 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/E | 0.6505 | likely_pathogenic | 0.5934 | pathogenic | -0.548 | Destabilizing | 0.994 | D | 0.393 | neutral | N | 0.487137175 | None | None | N |
| D/F | 0.9677 | likely_pathogenic | 0.9668 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/G | 0.7004 | likely_pathogenic | 0.6876 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.494094622 | None | None | N |
| D/H | 0.8837 | likely_pathogenic | 0.8688 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.634 | neutral | N | 0.498755884 | None | None | N |
| D/I | 0.9601 | likely_pathogenic | 0.9602 | pathogenic | 0.088 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/K | 0.9528 | likely_pathogenic | 0.9467 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| D/L | 0.9283 | likely_pathogenic | 0.9251 | pathogenic | 0.088 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/M | 0.971 | likely_pathogenic | 0.9702 | pathogenic | 0.414 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| D/N | 0.4554 | ambiguous | 0.4285 | ambiguous | -0.441 | Destabilizing | 1.0 | D | 0.623 | neutral | N | 0.510995469 | None | None | N |
| D/P | 0.9962 | likely_pathogenic | 0.9963 | pathogenic | -0.122 | Destabilizing | 0.998 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/Q | 0.922 | likely_pathogenic | 0.9103 | pathogenic | -0.377 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/R | 0.9427 | likely_pathogenic | 0.9357 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/S | 0.5734 | likely_pathogenic | 0.5405 | ambiguous | -0.598 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/T | 0.8552 | likely_pathogenic | 0.8441 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| D/V | 0.875 | likely_pathogenic | 0.8743 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.50078012 | None | None | N |
| D/W | 0.9904 | likely_pathogenic | 0.9904 | pathogenic | -0.163 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| D/Y | 0.8182 | likely_pathogenic | 0.814 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.511758031 | 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.