Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18756 | 56491;56492;56493 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| N2AB | 17115 | 51568;51569;51570 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| N2A | 16188 | 48787;48788;48789 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| N2B | 9691 | 29296;29297;29298 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| Novex-1 | 9816 | 29671;29672;29673 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| Novex-2 | 9883 | 29872;29873;29874 | chr2:178599635;178599634;178599633 | chr2:179464362;179464361;179464360 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 1.0 | N | 0.604 | 0.346 | 0.348101942276 | gnomAD-4.0.0 | 1.59387E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02792E-05 |
| R/K | rs1440402638  |
-0.194 | 0.997 | N | 0.487 | 0.313 | 0.280181792013 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/K | rs1440402638 |
-0.194 | 0.997 | N | 0.487 | 0.313 | 0.280181792013 | gnomAD-4.0.0 | 3.18827E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7259E-06 | 0 | 0 |
| R/T | None | None | 1.0 | N | 0.632 | 0.504 | 0.314417295294 | gnomAD-4.0.0 | 3.18827E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77685E-05 | None | 0 | 0 | 2.86295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.965 | likely_pathogenic | 0.9601 | pathogenic | -0.433 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| R/C | 0.743 | likely_pathogenic | 0.7142 | pathogenic | -0.411 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/D | 0.9861 | likely_pathogenic | 0.9864 | pathogenic | -0.026 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/E | 0.9243 | likely_pathogenic | 0.9168 | pathogenic | 0.062 | Stabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| R/F | 0.9727 | likely_pathogenic | 0.9652 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.9362 | likely_pathogenic | 0.9295 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.453427616 | None | None | N |
| R/H | 0.5208 | ambiguous | 0.495 | ambiguous | -1.054 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/I | 0.8631 | likely_pathogenic | 0.8331 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/K | 0.355 | ambiguous | 0.3369 | benign | -0.482 | Destabilizing | 0.997 | D | 0.487 | neutral | N | 0.474255517 | None | None | N |
| R/L | 0.8336 | likely_pathogenic | 0.8065 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| R/M | 0.9285 | likely_pathogenic | 0.9046 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | N | 0.463454022 | None | None | N |
| R/N | 0.9787 | likely_pathogenic | 0.9765 | pathogenic | 0.003 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| R/P | 0.9544 | likely_pathogenic | 0.9508 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/Q | 0.4921 | ambiguous | 0.4523 | ambiguous | -0.189 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| R/S | 0.9818 | likely_pathogenic | 0.9799 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.501615477 | None | None | N |
| R/T | 0.9518 | likely_pathogenic | 0.9435 | pathogenic | -0.366 | Destabilizing | 1.0 | D | 0.632 | neutral | N | 0.498921888 | None | None | N |
| R/V | 0.9159 | likely_pathogenic | 0.9055 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/W | 0.766 | likely_pathogenic | 0.7208 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.477799295 | None | None | N |
| R/Y | 0.9212 | likely_pathogenic | 0.9047 | pathogenic | 0.063 | Stabilizing | 1.0 | D | 0.705 | prob.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.