Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14397 | 43414;43415;43416 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| N2AB | 12756 | 38491;38492;38493 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| N2A | 11829 | 35710;35711;35712 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| N2B | 5332 | 16219;16220;16221 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| Novex-1 | 5457 | 16594;16595;16596 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| Novex-2 | 5524 | 16795;16796;16797 | chr2:178632942;178632941;178632940 | chr2:179497669;179497668;179497667 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1297192310  |
-0.293 | 0.012 | N | 0.422 | 0.149 | 0.154104182512 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| S/Y | rs1297192310 |
-0.291 | 0.989 | D | 0.809 | 0.398 | 0.255270683199 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| S/Y | rs1297192310 |
-0.291 | 0.989 | D | 0.809 | 0.398 | 0.255270683199 | gnomAD-4.0.0 | 1.59301E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43517E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2385 | likely_benign | 0.2032 | benign | -0.651 | Destabilizing | 0.622 | D | 0.631 | neutral | N | 0.519364996 | None | None | N |
| S/C | 0.3013 | likely_benign | 0.2179 | benign | -0.387 | Destabilizing | 0.012 | N | 0.422 | neutral | N | 0.438845561 | None | None | N |
| S/D | 0.9372 | likely_pathogenic | 0.9009 | pathogenic | 0.069 | Stabilizing | 0.725 | D | 0.727 | deleterious | None | None | None | None | N |
| S/E | 0.9533 | likely_pathogenic | 0.937 | pathogenic | 0.14 | Stabilizing | 0.841 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/F | 0.824 | likely_pathogenic | 0.7738 | pathogenic | -0.751 | Destabilizing | 0.989 | D | 0.814 | deleterious | D | 0.583832224 | None | None | N |
| S/G | 0.3434 | ambiguous | 0.2885 | benign | -0.963 | Destabilizing | 0.725 | D | 0.654 | prob.neutral | None | None | None | None | N |
| S/H | 0.8961 | likely_pathogenic | 0.8593 | pathogenic | -1.325 | Destabilizing | 0.993 | D | 0.779 | deleterious | None | None | None | None | N |
| S/I | 0.693 | likely_pathogenic | 0.6021 | pathogenic | 0.09 | Stabilizing | 0.974 | D | 0.801 | deleterious | None | None | None | None | N |
| S/K | 0.9874 | likely_pathogenic | 0.9832 | pathogenic | -0.274 | Destabilizing | 0.841 | D | 0.729 | deleterious | None | None | None | None | N |
| S/L | 0.5759 | likely_pathogenic | 0.4882 | ambiguous | 0.09 | Stabilizing | 0.841 | D | 0.789 | deleterious | None | None | None | None | N |
| S/M | 0.638 | likely_pathogenic | 0.5615 | ambiguous | 0.091 | Stabilizing | 0.998 | D | 0.773 | deleterious | None | None | None | None | N |
| S/N | 0.6261 | likely_pathogenic | 0.5023 | ambiguous | -0.476 | Destabilizing | 0.016 | N | 0.386 | neutral | None | None | None | None | N |
| S/P | 0.9851 | likely_pathogenic | 0.9773 | pathogenic | -0.121 | Destabilizing | 0.989 | D | 0.841 | deleterious | D | 0.544593889 | None | None | N |
| S/Q | 0.9447 | likely_pathogenic | 0.929 | pathogenic | -0.417 | Destabilizing | 0.974 | D | 0.779 | deleterious | None | None | None | None | N |
| S/R | 0.981 | likely_pathogenic | 0.9751 | pathogenic | -0.414 | Destabilizing | 0.949 | D | 0.823 | deleterious | None | None | None | None | N |
| S/T | 0.1762 | likely_benign | 0.136 | benign | -0.43 | Destabilizing | 0.799 | D | 0.67 | prob.neutral | N | 0.434274379 | None | None | N |
| S/V | 0.6116 | likely_pathogenic | 0.5288 | ambiguous | -0.121 | Destabilizing | 0.949 | D | 0.791 | deleterious | None | None | None | None | N |
| S/W | 0.9115 | likely_pathogenic | 0.8871 | pathogenic | -0.804 | Destabilizing | 0.998 | D | 0.806 | deleterious | None | None | None | None | N |
| S/Y | 0.7323 | likely_pathogenic | 0.6563 | pathogenic | -0.45 | Destabilizing | 0.989 | D | 0.809 | deleterious | D | 0.583832224 | 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.