Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14779 | 44560;44561;44562 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| N2AB | 13138 | 39637;39638;39639 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| N2A | 12211 | 36856;36857;36858 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| N2B | 5714 | 17365;17366;17367 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| Novex-1 | 5839 | 17740;17741;17742 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| Novex-2 | 5906 | 17941;17942;17943 | chr2:178629390;178629389;178629388 | chr2:179494117;179494116;179494115 |
| 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/A | None | None | 0.999 | N | 0.642 | 0.483 | 0.319114376414 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| E/K | rs1262894259  |
None | 0.999 | N | 0.612 | 0.435 | 0.24896430686 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs1262894259 |
None | 0.999 | N | 0.612 | 0.435 | 0.24896430686 | gnomAD-4.0.0 | 6.57479E-06 | None | None | None | None | N | None | 0 | 6.54279E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/Q | rs1262894259 |
None | 1.0 | N | 0.653 | 0.294 | 0.148003135375 | gnomAD-4.0.0 | 1.3691E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79962E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4366 | ambiguous | 0.4637 | ambiguous | -0.469 | Destabilizing | 0.999 | D | 0.642 | neutral | N | 0.496423779 | None | None | N |
| E/C | 0.9701 | likely_pathogenic | 0.9716 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| E/D | 0.2273 | likely_benign | 0.2398 | benign | -0.381 | Destabilizing | 0.999 | D | 0.475 | neutral | N | 0.453233806 | None | None | N |
| E/F | 0.9554 | likely_pathogenic | 0.9568 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/G | 0.3575 | ambiguous | 0.357 | ambiguous | -0.666 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.460912105 | None | None | N |
| E/H | 0.8298 | likely_pathogenic | 0.8216 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| E/I | 0.8811 | likely_pathogenic | 0.9123 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| E/K | 0.4143 | ambiguous | 0.4582 | ambiguous | 0.415 | Stabilizing | 0.999 | D | 0.612 | neutral | N | 0.447803985 | None | None | N |
| E/L | 0.8571 | likely_pathogenic | 0.8631 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| E/M | 0.7943 | likely_pathogenic | 0.815 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/N | 0.4926 | ambiguous | 0.5176 | ambiguous | 0.083 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| E/P | 0.9933 | likely_pathogenic | 0.9953 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| E/Q | 0.3168 | likely_benign | 0.3128 | benign | 0.105 | Stabilizing | 1.0 | D | 0.653 | neutral | N | 0.458117219 | None | None | N |
| E/R | 0.6473 | likely_pathogenic | 0.6604 | pathogenic | 0.514 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/S | 0.4719 | ambiguous | 0.4878 | ambiguous | -0.066 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| E/T | 0.62 | likely_pathogenic | 0.6876 | pathogenic | 0.098 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/V | 0.7068 | likely_pathogenic | 0.764 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | D | 0.63890278 | None | None | N |
| E/W | 0.9902 | likely_pathogenic | 0.991 | pathogenic | -0.273 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| E/Y | 0.9149 | likely_pathogenic | 0.9192 | pathogenic | -0.173 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.