Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33331 | 100216;100217;100218 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| N2AB | 31690 | 95293;95294;95295 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| N2A | 30763 | 92512;92513;92514 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| N2B | 24266 | 73021;73022;73023 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| Novex-1 | 24391 | 73396;73397;73398 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| Novex-2 | 24458 | 73597;73598;73599 | chr2:178537118;178537117;178537116 | chr2:179401845;179401844;179401843 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs56061641  |
-0.874 | 0.001 | N | 0.44 | 0.241 | None | gnomAD-2.1.1 | 2.61592E-04 | None | None | None | None | N | None | 2.90505E-04 | 6.53595E-04 | None | 0 | 0 | None | 3.61319E-04 | None | 0 | 2.03816E-04 | 8.44832E-04 |
| C/R | rs56061641 |
-0.874 | 0.001 | N | 0.44 | 0.241 | None | gnomAD-3.1.2 | 2.95885E-04 | None | None | None | None | N | None | 9.66E-05 | 1.1794E-03 | 0 | 0 | 0 | None | 0 | 1.58228E-02 | 1.91137E-04 | 2.07297E-04 | 1.91571E-03 |
| C/R | rs56061641 |
-0.874 | 0.001 | N | 0.44 | 0.241 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 5.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| C/R | rs56061641 |
-0.874 | 0.001 | N | 0.44 | 0.241 | None | gnomAD-4.0.0 | 2.12603E-04 | None | None | None | None | N | None | 2.5336E-04 | 7.3419E-04 | None | 0 | 0 | None | 0 | 1.35269E-02 | 1.17835E-04 | 3.62613E-04 | 4.1632E-04 |
| C/S | rs56061641 |
None | 0.425 | N | 0.511 | 0.199 | 0.511790803624 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/S | rs56061641 |
None | 0.425 | N | 0.511 | 0.199 | 0.511790803624 | gnomAD-4.0.0 | 2.47952E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3909E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4601 | ambiguous | 0.3458 | ambiguous | -1.56 | Destabilizing | 0.3 | N | 0.404 | neutral | None | None | None | None | N |
| C/D | 0.9001 | likely_pathogenic | 0.8138 | pathogenic | -1.238 | Destabilizing | 0.828 | D | 0.595 | neutral | None | None | None | None | N |
| C/E | 0.7623 | likely_pathogenic | 0.6557 | pathogenic | -1.003 | Destabilizing | 0.704 | D | 0.527 | neutral | None | None | None | None | N |
| C/F | 0.3067 | likely_benign | 0.2595 | benign | -0.917 | Destabilizing | 0.975 | D | 0.578 | neutral | N | 0.446618703 | None | None | N |
| C/G | 0.3147 | likely_benign | 0.2369 | benign | -1.919 | Destabilizing | 0.6 | D | 0.517 | neutral | N | 0.472573154 | None | None | N |
| C/H | 0.3661 | ambiguous | 0.2873 | benign | -2.046 | Highly Destabilizing | 0.944 | D | 0.611 | neutral | None | None | None | None | N |
| C/I | 0.6102 | likely_pathogenic | 0.4703 | ambiguous | -0.581 | Destabilizing | 0.828 | D | 0.605 | neutral | None | None | None | None | N |
| C/K | 0.3148 | likely_benign | 0.2637 | benign | -0.894 | Destabilizing | 0.329 | N | 0.539 | neutral | None | None | None | None | N |
| C/L | 0.4589 | ambiguous | 0.3835 | ambiguous | -0.581 | Destabilizing | 0.495 | N | 0.514 | neutral | None | None | None | None | N |
| C/M | 0.5655 | likely_pathogenic | 0.4802 | ambiguous | 0.328 | Stabilizing | 0.981 | D | 0.601 | neutral | None | None | None | None | N |
| C/N | 0.6323 | likely_pathogenic | 0.5023 | ambiguous | -1.495 | Destabilizing | 0.704 | D | 0.571 | neutral | None | None | None | None | N |
| C/P | 0.9963 | likely_pathogenic | 0.9941 | pathogenic | -0.886 | Destabilizing | 0.981 | D | 0.631 | neutral | None | None | None | None | N |
| C/Q | 0.2418 | likely_benign | 0.1887 | benign | -1.027 | Destabilizing | 0.704 | D | 0.576 | neutral | None | None | None | None | N |
| C/R | 0.0914 | likely_benign | 0.0794 | benign | -1.314 | Destabilizing | 0.001 | N | 0.44 | neutral | N | 0.329732818 | None | None | N |
| C/S | 0.4716 | ambiguous | 0.3349 | benign | -1.811 | Destabilizing | 0.425 | N | 0.511 | neutral | N | 0.439785945 | None | None | N |
| C/T | 0.5901 | likely_pathogenic | 0.4346 | ambiguous | -1.39 | Destabilizing | 0.665 | D | 0.506 | neutral | None | None | None | None | N |
| C/V | 0.4914 | ambiguous | 0.3639 | ambiguous | -0.886 | Destabilizing | 0.828 | D | 0.525 | neutral | None | None | None | None | N |
| C/W | 0.5726 | likely_pathogenic | 0.4921 | ambiguous | -1.277 | Destabilizing | 0.993 | D | 0.565 | neutral | N | 0.47187972 | None | None | N |
| C/Y | 0.3044 | likely_benign | 0.2366 | benign | -1.085 | Destabilizing | 0.975 | D | 0.577 | neutral | N | 0.466204542 | 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.