Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14376 | 43351;43352;43353 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| N2AB | 12735 | 38428;38429;38430 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| N2A | 11808 | 35647;35648;35649 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| N2B | 5311 | 16156;16157;16158 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| Novex-1 | 5436 | 16531;16532;16533 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| Novex-2 | 5503 | 16732;16733;16734 | chr2:178633005;178633004;178633003 | chr2:179497732;179497731;179497730 |
| 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/M | rs1559959762  |
None | 0.087 | N | 0.507 | 0.057 | 0.28492961333 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1559959762 |
None | 0.087 | N | 0.507 | 0.057 | 0.28492961333 | gnomAD-4.0.0 | 3.18555E-06 | None | None | None | None | N | None | 0 | 4.57477E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs181000791 |
-1.892 | None | N | 0.2 | 0.05 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/V | rs181000791 |
-1.892 | None | N | 0.2 | 0.05 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs181000791 |
-1.892 | None | N | 0.2 | 0.05 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/V | rs181000791 |
-1.892 | None | N | 0.2 | 0.05 | None | gnomAD-4.0.0 | 3.7194E-06 | None | None | None | None | N | None | 1.33316E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23941E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5433 | ambiguous | 0.5178 | ambiguous | -2.789 | Highly Destabilizing | 0.003 | N | 0.385 | neutral | None | None | None | None | N |
| I/C | 0.7336 | likely_pathogenic | 0.7462 | pathogenic | -1.89 | Destabilizing | 0.204 | N | 0.553 | neutral | None | None | None | None | N |
| I/D | 0.7927 | likely_pathogenic | 0.7763 | pathogenic | -3.328 | Highly Destabilizing | 0.204 | N | 0.642 | neutral | None | None | None | None | N |
| I/E | 0.6411 | likely_pathogenic | 0.6263 | pathogenic | -3.16 | Highly Destabilizing | 0.068 | N | 0.603 | neutral | None | None | None | None | N |
| I/F | 0.2042 | likely_benign | 0.2141 | benign | -1.699 | Destabilizing | 0.087 | N | 0.514 | neutral | D | 0.544593889 | None | None | N |
| I/G | 0.8252 | likely_pathogenic | 0.8193 | pathogenic | -3.249 | Highly Destabilizing | 0.068 | N | 0.58 | neutral | None | None | None | None | N |
| I/H | 0.4553 | ambiguous | 0.4592 | ambiguous | -2.719 | Highly Destabilizing | 0.747 | D | 0.639 | neutral | None | None | None | None | N |
| I/K | 0.3555 | ambiguous | 0.349 | ambiguous | -2.262 | Highly Destabilizing | 0.035 | N | 0.603 | neutral | None | None | None | None | N |
| I/L | 0.1589 | likely_benign | 0.1569 | benign | -1.453 | Destabilizing | 0.001 | N | 0.361 | neutral | N | 0.426695839 | None | None | N |
| I/M | 0.1614 | likely_benign | 0.1524 | benign | -1.211 | Destabilizing | 0.087 | N | 0.507 | neutral | N | 0.466195377 | None | None | N |
| I/N | 0.3482 | ambiguous | 0.3357 | benign | -2.467 | Highly Destabilizing | 0.162 | N | 0.627 | neutral | N | 0.506123541 | None | None | N |
| I/P | 0.975 | likely_pathogenic | 0.9782 | pathogenic | -1.884 | Destabilizing | 0.204 | N | 0.63 | neutral | None | None | None | None | N |
| I/Q | 0.4726 | ambiguous | 0.4622 | ambiguous | -2.408 | Highly Destabilizing | 0.439 | N | 0.625 | neutral | None | None | None | None | N |
| I/R | 0.2681 | likely_benign | 0.2691 | benign | -1.788 | Destabilizing | 0.204 | N | 0.633 | neutral | None | None | None | None | N |
| I/S | 0.3956 | ambiguous | 0.3869 | ambiguous | -3.035 | Highly Destabilizing | 0.013 | N | 0.544 | neutral | D | 0.54295631 | None | None | N |
| I/T | 0.2638 | likely_benign | 0.24 | benign | -2.76 | Highly Destabilizing | None | N | 0.345 | neutral | N | 0.419702494 | None | None | N |
| I/V | 0.0763 | likely_benign | 0.0756 | benign | -1.884 | Destabilizing | None | N | 0.2 | neutral | N | 0.431121596 | None | None | N |
| I/W | 0.8012 | likely_pathogenic | 0.8174 | pathogenic | -2.173 | Highly Destabilizing | 0.747 | D | 0.671 | prob.neutral | None | None | None | None | N |
| I/Y | 0.461 | ambiguous | 0.4693 | ambiguous | -1.983 | Destabilizing | 0.204 | N | 0.574 | 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.