Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18437 | 55534;55535;55536 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| N2AB | 16796 | 50611;50612;50613 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| N2A | 15869 | 47830;47831;47832 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| N2B | 9372 | 28339;28340;28341 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| Novex-1 | 9497 | 28714;28715;28716 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| Novex-2 | 9564 | 28915;28916;28917 | chr2:178601781;178601780;178601779 | chr2:179466508;179466507;179466506 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1378437369  |
None | None | D | 0.248 | 0.109 | 0.151104730317 | gnomAD-4.0.0 | 4.82531E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.4151E-06 | 0 | 1.67056E-05 |
| T/I | None | None | 0.491 | N | 0.614 | 0.301 | 0.466486631293 | gnomAD-4.0.0 | 1.61925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.49419E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0757 | likely_benign | 0.0799 | benign | -0.425 | Destabilizing | None | N | 0.248 | neutral | D | 0.523455839 | None | None | N |
| T/C | 0.3924 | ambiguous | 0.4065 | ambiguous | -0.218 | Destabilizing | 0.901 | D | 0.613 | neutral | None | None | None | None | N |
| T/D | 0.3127 | likely_benign | 0.3218 | benign | 0.146 | Stabilizing | 0.561 | D | 0.605 | neutral | None | None | None | None | N |
| T/E | 0.2583 | likely_benign | 0.2604 | benign | 0.062 | Stabilizing | 0.561 | D | 0.599 | neutral | None | None | None | None | N |
| T/F | 0.218 | likely_benign | 0.23 | benign | -0.946 | Destabilizing | 0.901 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/G | 0.2175 | likely_benign | 0.226 | benign | -0.543 | Destabilizing | 0.209 | N | 0.621 | neutral | None | None | None | None | N |
| T/H | 0.2332 | likely_benign | 0.2367 | benign | -0.821 | Destabilizing | 0.965 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/I | 0.1321 | likely_benign | 0.1324 | benign | -0.235 | Destabilizing | 0.491 | N | 0.614 | neutral | N | 0.506256945 | None | None | N |
| T/K | 0.1886 | likely_benign | 0.1877 | benign | -0.321 | Destabilizing | 0.561 | D | 0.595 | neutral | None | None | None | None | N |
| T/L | 0.094 | likely_benign | 0.1003 | benign | -0.235 | Destabilizing | 0.209 | N | 0.557 | neutral | None | None | None | None | N |
| T/M | 0.0773 | likely_benign | 0.0792 | benign | 0.016 | Stabilizing | 0.965 | D | 0.619 | neutral | None | None | None | None | N |
| T/N | 0.099 | likely_benign | 0.099 | benign | -0.055 | Destabilizing | 0.491 | N | 0.548 | neutral | N | 0.433297982 | None | None | N |
| T/P | 0.1488 | likely_benign | 0.1833 | benign | -0.271 | Destabilizing | 0.662 | D | 0.615 | neutral | N | 0.506603662 | None | None | N |
| T/Q | 0.2124 | likely_benign | 0.2156 | benign | -0.326 | Destabilizing | 0.901 | D | 0.629 | neutral | None | None | None | None | N |
| T/R | 0.1791 | likely_benign | 0.1875 | benign | -0.012 | Destabilizing | 0.561 | D | 0.622 | neutral | None | None | None | None | N |
| T/S | 0.1027 | likely_benign | 0.1054 | benign | -0.286 | Destabilizing | 0.002 | N | 0.26 | neutral | N | 0.430412392 | None | None | N |
| T/V | 0.1091 | likely_benign | 0.1113 | benign | -0.271 | Destabilizing | 0.209 | N | 0.51 | neutral | None | None | None | None | N |
| T/W | 0.5725 | likely_pathogenic | 0.5988 | pathogenic | -0.927 | Destabilizing | 0.991 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2486 | likely_benign | 0.2611 | benign | -0.65 | Destabilizing | 0.965 | D | 0.699 | prob.neutral | 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.