Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19664 | 59215;59216;59217 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| N2AB | 18023 | 54292;54293;54294 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| N2A | 17096 | 51511;51512;51513 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| N2B | 10599 | 32020;32021;32022 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| Novex-1 | 10724 | 32395;32396;32397 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| Novex-2 | 10791 | 32596;32597;32598 | chr2:178593218;178593217;178593216 | chr2:179457945;179457944;179457943 |
| 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 | rs769129424  |
-0.078 | 0.002 | N | 0.315 | 0.097 | 0.0401082797425 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 0 |
| D/E | rs769129424 |
-0.078 | 0.002 | N | 0.315 | 0.097 | 0.0401082797425 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/E | rs769129424 |
-0.078 | 0.002 | N | 0.315 | 0.097 | 0.0401082797425 | gnomAD-4.0.0 | 2.2934E-05 | None | None | None | None | I | None | 0 | 1.66789E-05 | None | 0 | 0 | None | 0 | 1.64636E-04 | 2.79752E-05 | 0 | 3.20318E-05 |
| D/N | rs921886474 |
None | 0.004 | N | 0.321 | 0.114 | 0.221019684889 | gnomAD-4.0.0 | 6.84362E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65711E-05 |
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 | 0.1831 | likely_benign | 0.1486 | benign | -0.187 | Destabilizing | 0.201 | N | 0.697 | prob.neutral | N | 0.479325768 | None | None | I |
| D/C | 0.6382 | likely_pathogenic | 0.5652 | pathogenic | 0.206 | Stabilizing | 0.982 | D | 0.759 | deleterious | None | None | None | None | I |
| D/E | 0.153 | likely_benign | 0.1336 | benign | -0.251 | Destabilizing | 0.002 | N | 0.315 | neutral | N | 0.446405273 | None | None | I |
| D/F | 0.5101 | ambiguous | 0.458 | ambiguous | -0.287 | Destabilizing | 0.982 | D | 0.741 | deleterious | None | None | None | None | I |
| D/G | 0.2865 | likely_benign | 0.232 | benign | -0.343 | Destabilizing | 0.201 | N | 0.699 | prob.neutral | N | 0.516419931 | None | None | I |
| D/H | 0.3417 | ambiguous | 0.2744 | benign | -0.133 | Destabilizing | 0.869 | D | 0.702 | prob.neutral | N | 0.471266653 | None | None | I |
| D/I | 0.2814 | likely_benign | 0.2333 | benign | 0.165 | Stabilizing | 0.826 | D | 0.76 | deleterious | None | None | None | None | I |
| D/K | 0.3147 | likely_benign | 0.238 | benign | 0.518 | Stabilizing | 0.25 | N | 0.731 | prob.delet. | None | None | None | None | I |
| D/L | 0.2896 | likely_benign | 0.2343 | benign | 0.165 | Stabilizing | 0.7 | D | 0.762 | deleterious | None | None | None | None | I |
| D/M | 0.5012 | ambiguous | 0.4536 | ambiguous | 0.316 | Stabilizing | 0.982 | D | 0.745 | deleterious | None | None | None | None | I |
| D/N | 0.1276 | likely_benign | 0.1141 | benign | 0.295 | Stabilizing | 0.004 | N | 0.321 | neutral | N | 0.502992061 | None | None | I |
| D/P | 0.431 | ambiguous | 0.3841 | ambiguous | 0.069 | Stabilizing | 0.826 | D | 0.754 | deleterious | None | None | None | None | I |
| D/Q | 0.3295 | likely_benign | 0.2769 | benign | 0.295 | Stabilizing | 0.539 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/R | 0.414 | ambiguous | 0.3323 | benign | 0.566 | Stabilizing | 0.539 | D | 0.771 | deleterious | None | None | None | None | I |
| D/S | 0.1667 | likely_benign | 0.1443 | benign | 0.208 | Stabilizing | 0.25 | N | 0.64 | neutral | None | None | None | None | I |
| D/T | 0.2779 | likely_benign | 0.237 | benign | 0.329 | Stabilizing | 0.7 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/V | 0.1891 | likely_benign | 0.15 | benign | 0.069 | Stabilizing | 0.638 | D | 0.763 | deleterious | N | 0.514131775 | None | None | I |
| D/W | 0.8612 | likely_pathogenic | 0.8327 | pathogenic | -0.207 | Destabilizing | 0.982 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/Y | 0.2078 | likely_benign | 0.1738 | benign | -0.055 | Destabilizing | 0.976 | D | 0.74 | deleterious | N | 0.488409856 | None | None | I |
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.