Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31735 | 95428;95429;95430 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| N2AB | 30094 | 90505;90506;90507 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| N2A | 29167 | 87724;87725;87726 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| N2B | 22670 | 68233;68234;68235 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| Novex-1 | 22795 | 68608;68609;68610 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| Novex-2 | 22862 | 68809;68810;68811 | chr2:178546033;178546032;178546031 | chr2:179410760;179410759;179410758 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 1.0 | N | 0.637 | 0.562 | 0.434272847907 | gnomAD-4.0.0 | 1.36847E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79898E-06 | 0 | 0 |
| D/V | rs760640290  |
0.191 | 1.0 | N | 0.712 | 0.595 | 0.744084085339 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/V | rs760640290 |
0.191 | 1.0 | N | 0.712 | 0.595 | 0.744084085339 | gnomAD-4.0.0 | 3.18276E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 3.02425E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.56 | ambiguous | 0.6936 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.489107872 | None | None | I |
| D/C | 0.9309 | likely_pathogenic | 0.9625 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| D/E | 0.5679 | likely_pathogenic | 0.7235 | pathogenic | -0.532 | Destabilizing | 1.0 | D | 0.447 | neutral | N | 0.503235655 | None | None | I |
| D/F | 0.9131 | likely_pathogenic | 0.9591 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| D/G | 0.5533 | ambiguous | 0.6796 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.506922639 | None | None | I |
| D/H | 0.7492 | likely_pathogenic | 0.8421 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.511758031 | None | None | I |
| D/I | 0.743 | likely_pathogenic | 0.8804 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/K | 0.8377 | likely_pathogenic | 0.9022 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/L | 0.8102 | likely_pathogenic | 0.8947 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| D/M | 0.8805 | likely_pathogenic | 0.941 | pathogenic | 0.649 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| D/N | 0.1398 | likely_benign | 0.1867 | benign | -0.205 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.500146544 | None | None | I |
| D/P | 0.9138 | likely_pathogenic | 0.9362 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/Q | 0.8098 | likely_pathogenic | 0.8908 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| D/R | 0.8661 | likely_pathogenic | 0.9192 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/S | 0.3392 | likely_benign | 0.4675 | ambiguous | -0.35 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/T | 0.4656 | ambiguous | 0.6318 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| D/V | 0.6031 | likely_pathogenic | 0.7668 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.519644843 | None | None | I |
| D/W | 0.9842 | likely_pathogenic | 0.9908 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| D/Y | 0.6249 | likely_pathogenic | 0.7367 | pathogenic | -0.13 | Destabilizing | 1.0 | D | 0.638 | neutral | D | 0.550372851 | 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.