Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30117 | 90574;90575;90576 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| N2AB | 28476 | 85651;85652;85653 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| N2A | 27549 | 82870;82871;82872 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| N2B | 21052 | 63379;63380;63381 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| Novex-1 | 21177 | 63754;63755;63756 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| Novex-2 | 21244 | 63955;63956;63957 | chr2:178552551;178552550;178552549 | chr2:179417278;179417277;179417276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1446752513  |
None | 0.008 | N | 0.438 | 0.171 | 0.400468435593 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs1446752513 |
None | 0.008 | N | 0.438 | 0.171 | 0.400468435593 | gnomAD-4.0.0 | 4.95759E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23105E-05 | None | 3.12432E-05 | 0 | 4.23794E-06 | 0 | 0 |
| I/V | rs1241230315 |
-1.227 | 0.001 | N | 0.222 | 0.09 | 0.269558022972 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs1241230315 |
-1.227 | 0.001 | N | 0.222 | 0.09 | 0.269558022972 | 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 |
| I/V | rs1241230315 |
-1.227 | 0.001 | N | 0.222 | 0.09 | 0.269558022972 | gnomAD-4.0.0 | 3.84357E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17879E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1344 | likely_benign | 0.1134 | benign | -1.816 | Destabilizing | 0.134 | N | 0.478 | neutral | None | None | None | None | N |
| I/C | 0.6596 | likely_pathogenic | 0.6702 | pathogenic | -1.2 | Destabilizing | 0.953 | D | 0.585 | neutral | None | None | None | None | N |
| I/D | 0.7643 | likely_pathogenic | 0.7701 | pathogenic | -1.243 | Destabilizing | 0.724 | D | 0.74 | deleterious | None | None | None | None | N |
| I/E | 0.5975 | likely_pathogenic | 0.6054 | pathogenic | -1.101 | Destabilizing | 0.428 | N | 0.725 | deleterious | None | None | None | None | N |
| I/F | 0.2079 | likely_benign | 0.1846 | benign | -0.953 | Destabilizing | 0.664 | D | 0.554 | neutral | N | 0.519862881 | None | None | N |
| I/G | 0.5967 | likely_pathogenic | 0.5825 | pathogenic | -2.279 | Highly Destabilizing | 0.272 | N | 0.693 | prob.delet. | None | None | None | None | N |
| I/H | 0.6309 | likely_pathogenic | 0.6198 | pathogenic | -1.481 | Destabilizing | 0.984 | D | 0.791 | deleterious | None | None | None | None | N |
| I/K | 0.4353 | ambiguous | 0.4575 | ambiguous | -1.283 | Destabilizing | 0.428 | N | 0.732 | deleterious | None | None | None | None | N |
| I/L | 0.105 | likely_benign | 0.1131 | benign | -0.547 | Destabilizing | 0.048 | N | 0.472 | neutral | N | 0.387279611 | None | None | N |
| I/M | 0.0887 | likely_benign | 0.0902 | benign | -0.538 | Destabilizing | 0.664 | D | 0.507 | neutral | N | 0.487617177 | None | None | N |
| I/N | 0.391 | ambiguous | 0.4268 | ambiguous | -1.394 | Destabilizing | 0.664 | D | 0.745 | deleterious | N | 0.474783953 | None | None | N |
| I/P | 0.8418 | likely_pathogenic | 0.7767 | pathogenic | -0.942 | Destabilizing | 0.842 | D | 0.763 | deleterious | None | None | None | None | N |
| I/Q | 0.5055 | ambiguous | 0.524 | ambiguous | -1.339 | Destabilizing | 0.842 | D | 0.771 | deleterious | None | None | None | None | N |
| I/R | 0.3446 | ambiguous | 0.3484 | ambiguous | -0.95 | Destabilizing | 0.724 | D | 0.772 | deleterious | None | None | None | None | N |
| I/S | 0.2354 | likely_benign | 0.236 | benign | -2.135 | Highly Destabilizing | 0.008 | N | 0.47 | neutral | N | 0.452733812 | None | None | N |
| I/T | 0.0808 | likely_benign | 0.0699 | benign | -1.845 | Destabilizing | 0.008 | N | 0.438 | neutral | N | 0.42077611 | None | None | N |
| I/V | 0.0611 | likely_benign | 0.0589 | benign | -0.942 | Destabilizing | 0.001 | N | 0.222 | neutral | N | 0.44467169 | None | None | N |
| I/W | 0.826 | likely_pathogenic | 0.7955 | pathogenic | -1.16 | Destabilizing | 0.984 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Y | 0.6177 | likely_pathogenic | 0.5979 | pathogenic | -0.872 | Destabilizing | 0.842 | D | 0.624 | 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.