Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24608 | 74047;74048;74049 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| N2AB | 22967 | 69124;69125;69126 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| N2A | 22040 | 66343;66344;66345 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| N2B | 15543 | 46852;46853;46854 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| Novex-1 | 15668 | 47227;47228;47229 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| Novex-2 | 15735 | 47428;47429;47430 | chr2:178572310;178572309;178572308 | chr2:179437037;179437036;179437035 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs750166986  |
-0.265 | None | N | 0.184 | 0.137 | 0.166414681773 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.13E-05 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.41084E-04 |
| A/T | rs750166986 |
-0.265 | None | N | 0.184 | 0.137 | 0.166414681773 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.41E-05 | 2.62192E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs750166986 |
-0.265 | None | N | 0.184 | 0.137 | 0.166414681773 | gnomAD-4.0.0 | 1.55176E-05 | None | None | None | None | N | None | 1.33583E-05 | 1.3352E-04 | None | 0 | 2.23704E-05 | None | 0 | 1.64908E-04 | 8.49072E-06 | 2.19771E-05 | 3.20842E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.2657 | likely_benign | 0.2503 | benign | -0.85 | Destabilizing | 0.721 | D | 0.599 | neutral | None | None | None | None | N |
| A/D | 0.1842 | likely_benign | 0.1645 | benign | -0.457 | Destabilizing | 0.107 | N | 0.626 | neutral | None | None | None | None | N |
| A/E | 0.1604 | likely_benign | 0.1437 | benign | -0.594 | Destabilizing | 0.025 | N | 0.567 | neutral | N | 0.462777448 | None | None | N |
| A/F | 0.2103 | likely_benign | 0.1829 | benign | -0.868 | Destabilizing | 0.611 | D | 0.727 | deleterious | None | None | None | None | N |
| A/G | 0.0905 | likely_benign | 0.0838 | benign | -0.298 | Destabilizing | 0.002 | N | 0.383 | neutral | N | 0.490868126 | None | None | N |
| A/H | 0.272 | likely_benign | 0.2541 | benign | -0.183 | Destabilizing | 0.761 | D | 0.649 | prob.neutral | None | None | None | None | N |
| A/I | 0.1092 | likely_benign | 0.1046 | benign | -0.397 | Destabilizing | 0.183 | N | 0.634 | neutral | None | None | None | None | N |
| A/K | 0.2132 | likely_benign | 0.1902 | benign | -0.586 | Destabilizing | 0.001 | N | 0.474 | neutral | None | None | None | None | N |
| A/L | 0.0854 | likely_benign | 0.0822 | benign | -0.397 | Destabilizing | 0.085 | N | 0.625 | neutral | None | None | None | None | N |
| A/M | 0.1105 | likely_benign | 0.1098 | benign | -0.646 | Destabilizing | 0.039 | N | 0.581 | neutral | None | None | None | None | N |
| A/N | 0.1237 | likely_benign | 0.1175 | benign | -0.308 | Destabilizing | 0.014 | N | 0.641 | neutral | None | None | None | None | N |
| A/P | 0.0859 | likely_benign | 0.0825 | benign | -0.329 | Destabilizing | None | N | 0.467 | neutral | N | 0.441652814 | None | None | N |
| A/Q | 0.1779 | likely_benign | 0.1724 | benign | -0.544 | Destabilizing | 0.309 | N | 0.705 | prob.delet. | None | None | None | None | N |
| A/R | 0.2337 | likely_benign | 0.2047 | benign | -0.15 | Destabilizing | 0.183 | N | 0.64 | neutral | None | None | None | None | N |
| A/S | 0.0736 | likely_benign | 0.0729 | benign | -0.512 | Destabilizing | None | N | 0.225 | neutral | N | 0.389471768 | None | None | N |
| A/T | 0.0623 | likely_benign | 0.0621 | benign | -0.572 | Destabilizing | None | N | 0.184 | neutral | N | 0.39789925 | None | None | N |
| A/V | 0.0739 | likely_benign | 0.073 | benign | -0.329 | Destabilizing | 0.002 | N | 0.191 | neutral | N | 0.411287048 | None | None | N |
| A/W | 0.4825 | ambiguous | 0.424 | ambiguous | -0.975 | Destabilizing | 0.973 | D | 0.739 | deleterious | None | None | None | None | N |
| A/Y | 0.2882 | likely_benign | 0.2535 | benign | -0.662 | Destabilizing | 0.906 | D | 0.687 | prob.delet. | 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.