Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7836 | 23731;23732;23733 | chr2:178720136;178720135;178720134 | chr2:179584863;179584862;179584861 |
| N2AB | 7519 | 22780;22781;22782 | chr2:178720136;178720135;178720134 | chr2:179584863;179584862;179584861 |
| N2A | 6592 | 19999;20000;20001 | chr2:178720136;178720135;178720134 | chr2:179584863;179584862;179584861 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/L | rs1312879712  |
None | 0.001 | N | 0.155 | 0.079 | 0.375861065471 | 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/L | rs1312879712 |
None | 0.001 | N | 0.155 | 0.079 | 0.375861065471 | gnomAD-4.0.0 | 3.04467E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61479E-06 | 0 | 0 |
| I/N | rs753936432 |
-2.557 | 0.963 | N | 0.729 | 0.668 | 0.87127155638 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.66963E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/N | rs753936432 |
-2.557 | 0.963 | N | 0.729 | 0.668 | 0.87127155638 | gnomAD-4.0.0 | 2.73694E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.55782E-05 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| I/T | None | None | 0.549 | N | 0.603 | 0.331 | 0.68026572208 | gnomAD-4.0.0 | 6.84235E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99514E-07 | 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 | 0.7631 | likely_pathogenic | 0.6503 | pathogenic | -2.282 | Highly Destabilizing | 0.25 | N | 0.601 | neutral | None | None | None | None | N |
| I/C | 0.9002 | likely_pathogenic | 0.8518 | pathogenic | -1.456 | Destabilizing | 0.977 | D | 0.639 | neutral | None | None | None | None | N |
| I/D | 0.9736 | likely_pathogenic | 0.9493 | pathogenic | -2.546 | Highly Destabilizing | 0.972 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/E | 0.9214 | likely_pathogenic | 0.8633 | pathogenic | -2.341 | Highly Destabilizing | 0.92 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/F | 0.2625 | likely_benign | 0.2269 | benign | -1.413 | Destabilizing | 0.81 | D | 0.635 | neutral | N | 0.501309185 | None | None | N |
| I/G | 0.9462 | likely_pathogenic | 0.8986 | pathogenic | -2.769 | Highly Destabilizing | 0.92 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/H | 0.8903 | likely_pathogenic | 0.8268 | pathogenic | -2.013 | Highly Destabilizing | 0.992 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/K | 0.874 | likely_pathogenic | 0.7982 | pathogenic | -1.814 | Destabilizing | 0.92 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/L | 0.1334 | likely_benign | 0.1186 | benign | -0.89 | Destabilizing | 0.001 | N | 0.155 | neutral | N | 0.436546144 | None | None | N |
| I/M | 0.1711 | likely_benign | 0.1439 | benign | -0.744 | Destabilizing | 0.81 | D | 0.652 | neutral | D | 0.536486638 | None | None | N |
| I/N | 0.8056 | likely_pathogenic | 0.7021 | pathogenic | -2.138 | Highly Destabilizing | 0.963 | D | 0.729 | prob.delet. | N | 0.510716934 | None | None | N |
| I/P | 0.9545 | likely_pathogenic | 0.9256 | pathogenic | -1.334 | Destabilizing | 0.972 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/Q | 0.8483 | likely_pathogenic | 0.7661 | pathogenic | -2.051 | Highly Destabilizing | 0.972 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/R | 0.8188 | likely_pathogenic | 0.7291 | pathogenic | -1.474 | Destabilizing | 0.92 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/S | 0.7999 | likely_pathogenic | 0.6851 | pathogenic | -2.77 | Highly Destabilizing | 0.81 | D | 0.678 | prob.neutral | N | 0.490295274 | None | None | N |
| I/T | 0.7034 | likely_pathogenic | 0.5713 | pathogenic | -2.421 | Highly Destabilizing | 0.549 | D | 0.603 | neutral | N | 0.495900681 | None | None | N |
| I/V | 0.1083 | likely_benign | 0.0894 | benign | -1.334 | Destabilizing | 0.002 | N | 0.169 | neutral | N | 0.433858129 | None | None | N |
| I/W | 0.8956 | likely_pathogenic | 0.862 | pathogenic | -1.713 | Destabilizing | 0.992 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7889 | likely_pathogenic | 0.7166 | pathogenic | -1.402 | Destabilizing | 0.92 | D | 0.709 | 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.