Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25333 | 76222;76223;76224 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| N2AB | 23692 | 71299;71300;71301 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| N2A | 22765 | 68518;68519;68520 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| N2B | 16268 | 49027;49028;49029 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| Novex-1 | 16393 | 49402;49403;49404 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| Novex-2 | 16460 | 49603;49604;49605 | chr2:178570135;178570134;178570133 | chr2:179434862;179434861;179434860 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | None | None | 1.0 | D | 0.739 | 0.576 | 0.505335117028 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 0 | 0 |
| G/S | rs757343393  |
-0.157 | 1.0 | N | 0.733 | 0.496 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-05 | 0 |
| G/S | rs757343393 |
-0.157 | 1.0 | N | 0.733 | 0.496 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| G/S | rs757343393 |
-0.157 | 1.0 | N | 0.733 | 0.496 | None | gnomAD-4.0.0 | 4.5246E-05 | None | None | None | None | I | None | 1.33554E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.76449E-05 | 2.19611E-05 | 3.20277E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.6973 | likely_pathogenic | 0.7661 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.513997574 | None | None | I |
| G/C | 0.6957 | likely_pathogenic | 0.8073 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.555018703 | None | None | I |
| G/D | 0.825 | likely_pathogenic | 0.8275 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.533431728 | None | None | I |
| G/E | 0.8813 | likely_pathogenic | 0.8872 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| G/F | 0.9535 | likely_pathogenic | 0.9667 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| G/H | 0.8629 | likely_pathogenic | 0.9033 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| G/I | 0.9517 | likely_pathogenic | 0.9572 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| G/K | 0.8513 | likely_pathogenic | 0.8839 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| G/L | 0.9324 | likely_pathogenic | 0.9534 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| G/M | 0.9433 | likely_pathogenic | 0.9605 | pathogenic | -0.481 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| G/N | 0.7496 | likely_pathogenic | 0.8026 | pathogenic | -0.17 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| G/P | 0.9953 | likely_pathogenic | 0.9945 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| G/Q | 0.8168 | likely_pathogenic | 0.8535 | pathogenic | -0.412 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| G/R | 0.7744 | likely_pathogenic | 0.8177 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.526532421 | None | None | I |
| G/S | 0.4704 | ambiguous | 0.5389 | ambiguous | -0.313 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.515643415 | None | None | I |
| G/T | 0.8589 | likely_pathogenic | 0.8789 | pathogenic | -0.397 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| G/V | 0.9186 | likely_pathogenic | 0.9319 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.548270754 | None | None | I |
| G/W | 0.9483 | likely_pathogenic | 0.9538 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| G/Y | 0.9147 | likely_pathogenic | 0.9367 | pathogenic | -0.702 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
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.