Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25681 | 77266;77267;77268 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| N2AB | 24040 | 72343;72344;72345 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| N2A | 23113 | 69562;69563;69564 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| N2B | 16616 | 50071;50072;50073 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| Novex-1 | 16741 | 50446;50447;50448 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| Novex-2 | 16808 | 50647;50648;50649 | chr2:178569091;178569090;178569089 | chr2:179433818;179433817;179433816 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs988101069  |
0.305 | 0.989 | N | 0.578 | 0.273 | 0.36036328697 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs988101069 |
0.305 | 0.989 | N | 0.578 | 0.273 | 0.36036328697 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs988101069 |
0.305 | 0.989 | N | 0.578 | 0.273 | 0.36036328697 | gnomAD-4.0.0 | 2.02998E-06 | None | None | None | None | I | None | 3.49406E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | None | None | 0.887 | N | 0.565 | 0.243 | 0.414930877219 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.846 | likely_pathogenic | 0.8186 | pathogenic | -0.8 | Destabilizing | 0.593 | D | 0.576 | neutral | None | None | None | None | I |
| Y/C | 0.3195 | likely_benign | 0.3133 | benign | 0.055 | Stabilizing | 0.989 | D | 0.578 | neutral | N | 0.47184931 | None | None | I |
| Y/D | 0.8714 | likely_pathogenic | 0.8513 | pathogenic | 0.924 | Stabilizing | 0.887 | D | 0.565 | neutral | N | 0.498116639 | None | None | I |
| Y/E | 0.9468 | likely_pathogenic | 0.9316 | pathogenic | 0.9 | Stabilizing | 0.836 | D | 0.567 | neutral | None | None | None | None | I |
| Y/F | 0.0836 | likely_benign | 0.089 | benign | -0.487 | Destabilizing | None | N | 0.375 | neutral | N | 0.480731277 | None | None | I |
| Y/G | 0.8861 | likely_pathogenic | 0.8529 | pathogenic | -0.983 | Destabilizing | 0.912 | D | 0.555 | neutral | None | None | None | None | I |
| Y/H | 0.4386 | ambiguous | 0.4107 | ambiguous | 0.16 | Stabilizing | 0.001 | N | 0.334 | neutral | N | 0.507243088 | None | None | I |
| Y/I | 0.5707 | likely_pathogenic | 0.5843 | pathogenic | -0.347 | Destabilizing | None | N | 0.349 | neutral | None | None | None | None | I |
| Y/K | 0.9422 | likely_pathogenic | 0.9326 | pathogenic | 0.219 | Stabilizing | 0.382 | N | 0.574 | neutral | None | None | None | None | I |
| Y/L | 0.6723 | likely_pathogenic | 0.6621 | pathogenic | -0.347 | Destabilizing | 0.004 | N | 0.493 | neutral | None | None | None | None | I |
| Y/M | 0.7301 | likely_pathogenic | 0.7448 | pathogenic | -0.102 | Destabilizing | 0.606 | D | 0.509 | neutral | None | None | None | None | I |
| Y/N | 0.4661 | ambiguous | 0.4515 | ambiguous | 0.061 | Stabilizing | 0.794 | D | 0.577 | neutral | N | 0.52163375 | None | None | I |
| Y/P | 0.9924 | likely_pathogenic | 0.9916 | pathogenic | -0.478 | Destabilizing | 0.969 | D | 0.557 | neutral | None | None | None | None | I |
| Y/Q | 0.8862 | likely_pathogenic | 0.8682 | pathogenic | 0.055 | Stabilizing | 0.757 | D | 0.515 | neutral | None | None | None | None | I |
| Y/R | 0.8978 | likely_pathogenic | 0.8825 | pathogenic | 0.557 | Stabilizing | 0.68 | D | 0.583 | neutral | None | None | None | None | I |
| Y/S | 0.748 | likely_pathogenic | 0.7127 | pathogenic | -0.427 | Destabilizing | 0.887 | D | 0.565 | neutral | N | 0.472632551 | None | None | I |
| Y/T | 0.8644 | likely_pathogenic | 0.8447 | pathogenic | -0.36 | Destabilizing | 0.836 | D | 0.57 | neutral | None | None | None | None | I |
| Y/V | 0.5624 | ambiguous | 0.5604 | ambiguous | -0.478 | Destabilizing | 0.201 | N | 0.487 | neutral | None | None | None | None | I |
| Y/W | 0.55 | ambiguous | 0.5604 | ambiguous | -0.567 | Destabilizing | 0.985 | D | 0.464 | neutral | 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.