Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9201 | 27826;27827;27828 | chr2:178712321;178712320;178712319 | chr2:179577048;179577047;179577046 |
| N2AB | 8884 | 26875;26876;26877 | chr2:178712321;178712320;178712319 | chr2:179577048;179577047;179577046 |
| N2A | 7957 | 24094;24095;24096 | chr2:178712321;178712320;178712319 | chr2:179577048;179577047;179577046 |
| 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/K | rs911557684  |
None | 0.971 | N | 0.667 | 0.555 | 0.601684871619 | 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/K | rs911557684 |
None | 0.971 | N | 0.667 | 0.555 | 0.601684871619 | gnomAD-4.0.0 | 2.02988E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40982E-06 | 0 | 0 |
| I/M | rs2154295981 |
None | 0.942 | N | 0.535 | 0.38 | 0.285316908763 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | None | None | 0.006 | N | 0.258 | 0.068 | 0.15556083564 | gnomAD-4.0.0 | 6.84793E-07 | None | None | None | None | N | None | 2.99258E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.6577 | likely_pathogenic | 0.6526 | pathogenic | -1.886 | Destabilizing | 0.754 | D | 0.456 | neutral | None | None | None | None | N |
| I/C | 0.8325 | likely_pathogenic | 0.8274 | pathogenic | -1.288 | Destabilizing | 0.994 | D | 0.568 | neutral | None | None | None | None | N |
| I/D | 0.9407 | likely_pathogenic | 0.9377 | pathogenic | -1.134 | Destabilizing | 0.993 | D | 0.655 | neutral | None | None | None | None | N |
| I/E | 0.9097 | likely_pathogenic | 0.9059 | pathogenic | -1.067 | Destabilizing | 0.978 | D | 0.667 | neutral | None | None | None | None | N |
| I/F | 0.3101 | likely_benign | 0.2761 | benign | -1.223 | Destabilizing | 0.956 | D | 0.563 | neutral | None | None | None | None | N |
| I/G | 0.8873 | likely_pathogenic | 0.8849 | pathogenic | -2.258 | Highly Destabilizing | 0.978 | D | 0.666 | neutral | None | None | None | None | N |
| I/H | 0.8429 | likely_pathogenic | 0.8277 | pathogenic | -1.45 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| I/K | 0.8572 | likely_pathogenic | 0.853 | pathogenic | -1.094 | Destabilizing | 0.971 | D | 0.667 | neutral | N | 0.49809605 | None | None | N |
| I/L | 0.1442 | likely_benign | 0.148 | benign | -0.9 | Destabilizing | 0.294 | N | 0.374 | neutral | N | 0.473355523 | None | None | N |
| I/M | 0.1821 | likely_benign | 0.1769 | benign | -0.87 | Destabilizing | 0.942 | D | 0.535 | neutral | N | 0.497842561 | None | None | N |
| I/N | 0.5566 | ambiguous | 0.5483 | ambiguous | -0.997 | Destabilizing | 0.993 | D | 0.661 | neutral | None | None | None | None | N |
| I/P | 0.8265 | likely_pathogenic | 0.8238 | pathogenic | -1.201 | Destabilizing | 0.993 | D | 0.659 | neutral | None | None | None | None | N |
| I/Q | 0.8303 | likely_pathogenic | 0.8272 | pathogenic | -1.108 | Destabilizing | 0.993 | D | 0.667 | neutral | None | None | None | None | N |
| I/R | 0.7988 | likely_pathogenic | 0.7955 | pathogenic | -0.664 | Destabilizing | 0.971 | D | 0.663 | neutral | N | 0.49809605 | None | None | N |
| I/S | 0.5911 | likely_pathogenic | 0.5837 | pathogenic | -1.749 | Destabilizing | 0.956 | D | 0.573 | neutral | None | None | None | None | N |
| I/T | 0.4439 | ambiguous | 0.4239 | ambiguous | -1.562 | Destabilizing | 0.822 | D | 0.501 | neutral | N | 0.485979276 | None | None | N |
| I/V | 0.0891 | likely_benign | 0.0864 | benign | -1.201 | Destabilizing | 0.006 | N | 0.258 | neutral | N | 0.392676204 | None | None | N |
| I/W | 0.9434 | likely_pathogenic | 0.936 | pathogenic | -1.299 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| I/Y | 0.7701 | likely_pathogenic | 0.7568 | pathogenic | -1.053 | Destabilizing | 0.978 | D | 0.543 | 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.