Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2707 | 8344;8345;8346 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| N2AB | 2707 | 8344;8345;8346 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| N2A | 2707 | 8344;8345;8346 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| N2B | 2661 | 8206;8207;8208 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| Novex-1 | 2661 | 8206;8207;8208 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| Novex-2 | 2661 | 8206;8207;8208 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
| Novex-3 | 2707 | 8344;8345;8346 | chr2:178770673;178770672;178770671 | chr2:179635400;179635399;179635398 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs376758159  |
-0.008 | 0.997 | D | 0.501 | 0.448 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 1.32252E-04 | 7.77E-06 | 0 |
| V/I | rs376758159 |
-0.008 | 0.997 | D | 0.501 | 0.448 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs376758159 |
-0.008 | 0.997 | D | 0.501 | 0.448 | None | gnomAD-4.0.0 | 9.00518E-06 | None | None | None | None | N | None | 1.69233E-05 | 0 | None | 0 | 0 | None | 6.62208E-05 | 0 | 2.39202E-06 | 0 | 2.8456E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4704 | ambiguous | 0.6558 | pathogenic | -0.887 | Destabilizing | 0.999 | D | 0.558 | neutral | D | 0.635931026 | None | None | N |
| V/C | 0.9366 | likely_pathogenic | 0.9653 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| V/D | 0.9257 | likely_pathogenic | 0.9774 | pathogenic | -0.808 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.673374356 | None | None | N |
| V/E | 0.8346 | likely_pathogenic | 0.9318 | pathogenic | -0.82 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| V/F | 0.5676 | likely_pathogenic | 0.7337 | pathogenic | -0.744 | Destabilizing | 1.0 | D | 0.62 | neutral | D | 0.673899984 | None | None | N |
| V/G | 0.6137 | likely_pathogenic | 0.8131 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.67329027 | None | None | N |
| V/H | 0.97 | likely_pathogenic | 0.9886 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/I | 0.1104 | likely_benign | 0.1175 | benign | -0.377 | Destabilizing | 0.997 | D | 0.501 | neutral | D | 0.548730219 | None | None | N |
| V/K | 0.8956 | likely_pathogenic | 0.9597 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| V/L | 0.4778 | ambiguous | 0.6024 | pathogenic | -0.377 | Destabilizing | 0.997 | D | 0.573 | neutral | D | 0.581847604 | None | None | N |
| V/M | 0.3666 | ambiguous | 0.5183 | ambiguous | -0.652 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| V/N | 0.861 | likely_pathogenic | 0.943 | pathogenic | -0.637 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/P | 0.8266 | likely_pathogenic | 0.8565 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| V/Q | 0.8577 | likely_pathogenic | 0.9397 | pathogenic | -0.761 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/R | 0.868 | likely_pathogenic | 0.9457 | pathogenic | -0.304 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/S | 0.681 | likely_pathogenic | 0.8449 | pathogenic | -1.037 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| V/T | 0.5616 | ambiguous | 0.7178 | pathogenic | -0.934 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| V/W | 0.983 | likely_pathogenic | 0.9927 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| V/Y | 0.9395 | likely_pathogenic | 0.9726 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.622 | 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.