Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22612 | 68059;68060;68061 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| N2AB | 20971 | 63136;63137;63138 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| N2A | 20044 | 60355;60356;60357 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| N2B | 13547 | 40864;40865;40866 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| Novex-1 | 13672 | 41239;41240;41241 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| Novex-2 | 13739 | 41440;41441;41442 | chr2:178579196;178579195;178579194 | chr2:179443923;179443922;179443921 |
| 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/G | None | None | 1.0 | N | 0.695 | 0.478 | 0.28492961333 | gnomAD-4.0.0 | 1.59178E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8594E-06 | 0 | 0 |
| D/N | rs757888367  |
-0.601 | 1.0 | N | 0.643 | 0.364 | 0.235664433957 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| D/N | rs757888367 |
-0.601 | 1.0 | N | 0.643 | 0.364 | 0.235664433957 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/N | rs757888367 |
-0.601 | 1.0 | N | 0.643 | 0.364 | 0.235664433957 | gnomAD-4.0.0 | 2.1074E-05 | None | None | None | None | N | None | 1.33554E-05 | 1.6675E-05 | None | 0 | 2.23164E-05 | None | 0 | 0 | 2.45846E-05 | 2.19597E-05 | 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 | 0.3023 | likely_benign | 0.2365 | benign | -0.101 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.508946881 | None | None | N |
| D/C | 0.7804 | likely_pathogenic | 0.7159 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| D/E | 0.2419 | likely_benign | 0.2016 | benign | -0.663 | Destabilizing | 1.0 | D | 0.453 | neutral | N | 0.480336127 | None | None | N |
| D/F | 0.8212 | likely_pathogenic | 0.7628 | pathogenic | -0.512 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| D/G | 0.2365 | likely_benign | 0.1744 | benign | -0.332 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.483376432 | None | None | N |
| D/H | 0.4318 | ambiguous | 0.3566 | ambiguous | -0.863 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.507312085 | None | None | N |
| D/I | 0.7478 | likely_pathogenic | 0.6957 | pathogenic | 0.459 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| D/K | 0.5651 | likely_pathogenic | 0.4502 | ambiguous | None | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/L | 0.6765 | likely_pathogenic | 0.5939 | pathogenic | 0.459 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| D/M | 0.8509 | likely_pathogenic | 0.8075 | pathogenic | 0.876 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/N | 0.1288 | likely_benign | 0.0969 | benign | -0.158 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.436542491 | None | None | N |
| D/P | 0.9172 | likely_pathogenic | 0.8831 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/Q | 0.4559 | ambiguous | 0.3847 | ambiguous | -0.122 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| D/R | 0.5577 | ambiguous | 0.4617 | ambiguous | -0.102 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| D/S | 0.2027 | likely_benign | 0.1575 | benign | -0.3 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| D/T | 0.4857 | ambiguous | 0.4153 | ambiguous | -0.128 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/V | 0.5564 | ambiguous | 0.4973 | ambiguous | 0.297 | Stabilizing | 1.0 | D | 0.791 | deleterious | N | 0.455188816 | None | None | N |
| D/W | 0.9524 | likely_pathogenic | 0.9394 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/Y | 0.425 | ambiguous | 0.3425 | ambiguous | -0.342 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.459708267 | 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.