Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32342 | 97249;97250;97251 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| N2AB | 30701 | 92326;92327;92328 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| N2A | 29774 | 89545;89546;89547 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| N2B | 23277 | 70054;70055;70056 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| Novex-1 | 23402 | 70429;70430;70431 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| Novex-2 | 23469 | 70630;70631;70632 | chr2:178542830;178542829;178542828 | chr2:179407557;179407556;179407555 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1559116130  |
None | 0.046 | N | 0.263 | 0.126 | 0.197625483188 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| F/L | rs1559116130 |
None | 0.046 | N | 0.263 | 0.126 | 0.197625483188 | 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 |
| F/L | rs1559116130 |
None | 0.046 | N | 0.263 | 0.126 | 0.197625483188 | gnomAD-4.0.0 | 3.84326E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17892E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7069 | likely_pathogenic | 0.5798 | pathogenic | -1.802 | Destabilizing | 0.953 | D | 0.589 | neutral | None | None | None | None | N |
| F/C | 0.3959 | ambiguous | 0.3302 | benign | -1.084 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | N | 0.47046585 | None | None | N |
| F/D | 0.9449 | likely_pathogenic | 0.9146 | pathogenic | 0.338 | Stabilizing | 0.998 | D | 0.747 | deleterious | None | None | None | None | N |
| F/E | 0.9319 | likely_pathogenic | 0.9069 | pathogenic | 0.433 | Stabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/G | 0.9013 | likely_pathogenic | 0.8373 | pathogenic | -2.123 | Highly Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| F/H | 0.4725 | ambiguous | 0.4059 | ambiguous | -0.433 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| F/I | 0.3756 | ambiguous | 0.2772 | benign | -0.86 | Destabilizing | 0.885 | D | 0.477 | neutral | N | 0.484413795 | None | None | N |
| F/K | 0.7996 | likely_pathogenic | 0.7886 | pathogenic | -0.784 | Destabilizing | 0.993 | D | 0.733 | prob.delet. | None | None | None | None | N |
| F/L | 0.8278 | likely_pathogenic | 0.752 | pathogenic | -0.86 | Destabilizing | 0.046 | N | 0.263 | neutral | N | 0.45886199 | None | None | N |
| F/M | 0.6392 | likely_pathogenic | 0.5634 | ambiguous | -0.761 | Destabilizing | 0.986 | D | 0.613 | neutral | None | None | None | None | N |
| F/N | 0.8233 | likely_pathogenic | 0.7402 | pathogenic | -0.816 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| F/P | 0.9947 | likely_pathogenic | 0.9904 | pathogenic | -1.165 | Destabilizing | 0.998 | D | 0.754 | deleterious | None | None | None | None | N |
| F/Q | 0.7551 | likely_pathogenic | 0.6953 | pathogenic | -0.788 | Destabilizing | 0.998 | D | 0.754 | deleterious | None | None | None | None | N |
| F/R | 0.6548 | likely_pathogenic | 0.633 | pathogenic | -0.309 | Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| F/S | 0.5898 | likely_pathogenic | 0.4346 | ambiguous | -1.757 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | N | 0.503615632 | None | None | N |
| F/T | 0.7351 | likely_pathogenic | 0.5976 | pathogenic | -1.563 | Destabilizing | 0.993 | D | 0.654 | neutral | None | None | None | None | N |
| F/V | 0.3385 | likely_benign | 0.2485 | benign | -1.165 | Destabilizing | 0.885 | D | 0.526 | neutral | N | 0.478314542 | None | None | N |
| F/W | 0.5732 | likely_pathogenic | 0.5303 | ambiguous | -0.097 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| F/Y | 0.157 | likely_benign | 0.1402 | benign | -0.303 | Destabilizing | 0.969 | D | 0.535 | neutral | N | 0.466001393 | 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.