Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21806 | 65641;65642;65643 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| N2AB | 20165 | 60718;60719;60720 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| N2A | 19238 | 57937;57938;57939 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| N2B | 12741 | 38446;38447;38448 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| Novex-1 | 12866 | 38821;38822;38823 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| Novex-2 | 12933 | 39022;39023;39024 | chr2:178583766;178583765;178583764 | chr2:179448493;179448492;179448491 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | rs771120053  |
None | 0.996 | N | 0.732 | 0.377 | 0.573850641692 | gnomAD-4.0.0 | 6.85245E-07 | None | None | None | None | N | None | 0 | 2.24598E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs771120053 |
-0.328 | 0.997 | N | 0.607 | 0.323 | 0.252681307341 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 5.86E-05 | None | 0 | 0 | None | 3.32E-05 | None | 0 | 0 | 0 |
| R/Q | rs771120053 |
-0.328 | 0.997 | N | 0.607 | 0.323 | 0.252681307341 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs771120053 |
-0.328 | 0.997 | N | 0.607 | 0.323 | 0.252681307341 | gnomAD-4.0.0 | 5.58548E-06 | None | None | None | None | N | None | 1.33643E-05 | 3.34594E-05 | None | 0 | 0 | None | 0 | 0 | 2.545E-06 | 3.30739E-05 | 0 |
| R/W | rs778703530 |
-0.431 | 1.0 | N | 0.658 | 0.327 | None | gnomAD-2.1.1 | 8.33E-05 | None | None | None | None | N | None | 4.19E-05 | 5.73E-05 | None | 2.9383E-04 | 1.05186E-04 | None | 0 | None | 0 | 1.18997E-04 | 0 |
| R/W | rs778703530 |
-0.431 | 1.0 | N | 0.658 | 0.327 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 7.24E-05 | 6.56E-05 | 0 | 5.76037E-04 | 0 | None | 0 | 0 | 1.02987E-04 | 0 | 0 |
| R/W | rs778703530 |
-0.431 | 1.0 | N | 0.658 | 0.327 | None | gnomAD-4.0.0 | 8.81411E-05 | None | None | None | None | N | None | 5.34531E-05 | 8.37212E-05 | None | 3.04857E-04 | 1.57169E-04 | None | 0 | 0 | 7.97544E-05 | 9.92676E-05 | 2.24604E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7747 | likely_pathogenic | 0.759 | pathogenic | -0.786 | Destabilizing | 0.953 | D | 0.545 | neutral | None | None | None | None | N |
| R/C | 0.3241 | likely_benign | 0.3193 | benign | -0.646 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/D | 0.9568 | likely_pathogenic | 0.9451 | pathogenic | 0.021 | Stabilizing | 0.986 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/E | 0.8254 | likely_pathogenic | 0.797 | pathogenic | 0.166 | Stabilizing | 0.91 | D | 0.478 | neutral | None | None | None | None | N |
| R/F | 0.8286 | likely_pathogenic | 0.8121 | pathogenic | -0.508 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.767 | likely_pathogenic | 0.7485 | pathogenic | -1.123 | Destabilizing | 0.975 | D | 0.626 | neutral | N | 0.470394506 | None | None | N |
| R/H | 0.2645 | likely_benign | 0.2391 | benign | -1.49 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| R/I | 0.5395 | ambiguous | 0.5165 | ambiguous | 0.125 | Stabilizing | 0.993 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/K | 0.1952 | likely_benign | 0.1784 | benign | -0.699 | Destabilizing | 0.06 | N | 0.327 | neutral | None | None | None | None | N |
| R/L | 0.4284 | ambiguous | 0.413 | ambiguous | 0.125 | Stabilizing | 0.975 | D | 0.626 | neutral | N | 0.513555772 | None | None | N |
| R/M | 0.6113 | likely_pathogenic | 0.5914 | pathogenic | -0.256 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/N | 0.9005 | likely_pathogenic | 0.8879 | pathogenic | -0.211 | Destabilizing | 0.986 | D | 0.607 | neutral | None | None | None | None | N |
| R/P | 0.6019 | likely_pathogenic | 0.5748 | pathogenic | -0.158 | Destabilizing | 0.996 | D | 0.732 | prob.delet. | N | 0.487715965 | None | None | N |
| R/Q | 0.2306 | likely_benign | 0.2129 | benign | -0.314 | Destabilizing | 0.997 | D | 0.607 | neutral | N | 0.475170742 | None | None | N |
| R/S | 0.8874 | likely_pathogenic | 0.8715 | pathogenic | -0.977 | Destabilizing | 0.953 | D | 0.643 | neutral | None | None | None | None | N |
| R/T | 0.7002 | likely_pathogenic | 0.6748 | pathogenic | -0.635 | Destabilizing | 0.986 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/V | 0.6462 | likely_pathogenic | 0.6247 | pathogenic | -0.158 | Destabilizing | 0.993 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/W | 0.4302 | ambiguous | 0.4018 | ambiguous | -0.159 | Destabilizing | 1.0 | D | 0.658 | neutral | N | 0.504374517 | None | None | N |
| R/Y | 0.7013 | likely_pathogenic | 0.6785 | pathogenic | 0.115 | Stabilizing | 0.998 | D | 0.723 | 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.