Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15306 | 46141;46142;46143 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| N2AB | 13665 | 41218;41219;41220 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| N2A | 12738 | 38437;38438;38439 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| N2B | 6241 | 18946;18947;18948 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| Novex-1 | 6366 | 19321;19322;19323 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| Novex-2 | 6433 | 19522;19523;19524 | chr2:178620605;178620604;178620603 | chr2:179485332;179485331;179485330 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs761792062  |
-0.534 | 0.993 | N | 0.463 | 0.201 | 0.353761421236 | gnomAD-2.1.1 | 1.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.71E-05 | 0 |
| E/D | rs761792062 |
-0.534 | 0.993 | N | 0.463 | 0.201 | 0.353761421236 | gnomAD-4.0.0 | 1.2352E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.62151E-05 | 0 | 0 |
| E/K | rs774339883 |
0.131 | 0.993 | N | 0.505 | 0.339 | 0.348764635752 | gnomAD-2.1.1 | 1.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.71E-05 | 0 |
| E/K | rs774339883 |
0.131 | 0.993 | N | 0.505 | 0.339 | 0.348764635752 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| E/K | rs774339883 |
0.131 | 0.993 | N | 0.505 | 0.339 | 0.348764635752 | gnomAD-4.0.0 | 3.79034E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.09315E-05 | 0 | 1.60736E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2923 | likely_benign | 0.2535 | benign | -0.637 | Destabilizing | 0.91 | D | 0.552 | neutral | N | 0.505199458 | None | None | N |
| E/C | 0.8917 | likely_pathogenic | 0.9074 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| E/D | 0.2468 | likely_benign | 0.2449 | benign | -0.819 | Destabilizing | 0.993 | D | 0.463 | neutral | N | 0.507700699 | None | None | N |
| E/F | 0.7925 | likely_pathogenic | 0.7893 | pathogenic | -0.001 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | None | None | None | None | N |
| E/G | 0.479 | ambiguous | 0.3769 | ambiguous | -0.957 | Destabilizing | 0.993 | D | 0.563 | neutral | N | 0.511726249 | None | None | N |
| E/H | 0.6365 | likely_pathogenic | 0.6395 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | N |
| E/I | 0.3771 | ambiguous | 0.4079 | ambiguous | 0.221 | Stabilizing | 0.942 | D | 0.571 | neutral | None | None | None | None | N |
| E/K | 0.369 | ambiguous | 0.2837 | benign | -0.294 | Destabilizing | 0.993 | D | 0.505 | neutral | N | 0.426678529 | None | None | N |
| E/L | 0.5382 | ambiguous | 0.5342 | ambiguous | 0.221 | Stabilizing | 0.942 | D | 0.582 | neutral | None | None | None | None | N |
| E/M | 0.5505 | ambiguous | 0.5474 | ambiguous | 0.355 | Stabilizing | 0.996 | D | 0.704 | prob.neutral | None | None | None | None | N |
| E/N | 0.4892 | ambiguous | 0.4644 | ambiguous | -0.887 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | N |
| E/P | 0.968 | likely_pathogenic | 0.9608 | pathogenic | -0.044 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| E/Q | 0.2346 | likely_benign | 0.2056 | benign | -0.758 | Destabilizing | 0.993 | D | 0.487 | neutral | N | 0.479357866 | None | None | N |
| E/R | 0.5036 | ambiguous | 0.4605 | ambiguous | 0.114 | Stabilizing | 0.999 | D | 0.552 | neutral | None | None | None | None | N |
| E/S | 0.3503 | ambiguous | 0.3196 | benign | -1.094 | Destabilizing | 0.985 | D | 0.48 | neutral | None | None | None | None | N |
| E/T | 0.3296 | likely_benign | 0.3234 | benign | -0.824 | Destabilizing | 0.97 | D | 0.537 | neutral | None | None | None | None | N |
| E/V | 0.227 | likely_benign | 0.2439 | benign | -0.044 | Destabilizing | 0.122 | N | 0.341 | neutral | N | 0.463611292 | None | None | N |
| E/W | 0.947 | likely_pathogenic | 0.9451 | pathogenic | 0.282 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| E/Y | 0.7294 | likely_pathogenic | 0.7169 | pathogenic | 0.258 | Stabilizing | 0.999 | D | 0.691 | prob.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.