Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15899 | 47920;47921;47922 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| N2AB | 14258 | 42997;42998;42999 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| N2A | 13331 | 40216;40217;40218 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| N2B | 6834 | 20725;20726;20727 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| Novex-1 | 6959 | 21100;21101;21102 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| Novex-2 | 7026 | 21301;21302;21303 | chr2:178617390;178617389;178617388 | chr2:179482117;179482116;179482115 |
| 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 | rs1232133882  |
-1.364 | None | N | 0.441 | 0.133 | 0.404453528171 | gnomAD-2.1.1 | 9.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.24704E-04 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs1232133882 |
-1.364 | None | N | 0.441 | 0.133 | 0.404453528171 | 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/R | rs1232133882 |
-1.364 | None | N | 0.441 | 0.133 | 0.404453528171 | gnomAD-4.0.0 | 3.1449E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.78273E-05 | None | 0 | 0 | 1.70807E-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 | 0.3675 | ambiguous | 0.4581 | ambiguous | -1.388 | Destabilizing | 0.007 | N | 0.389 | neutral | None | None | None | None | N |
| C/D | 0.8113 | likely_pathogenic | 0.8721 | pathogenic | -1.323 | Destabilizing | 0.072 | N | 0.589 | neutral | None | None | None | None | N |
| C/E | 0.6795 | likely_pathogenic | 0.7648 | pathogenic | -1.074 | Destabilizing | 0.016 | N | 0.54 | neutral | None | None | None | None | N |
| C/F | 0.3282 | likely_benign | 0.403 | ambiguous | -0.835 | Destabilizing | 0.295 | N | 0.587 | neutral | N | 0.480616749 | None | None | N |
| C/G | 0.2367 | likely_benign | 0.3054 | benign | -1.728 | Destabilizing | 0.055 | N | 0.563 | neutral | N | 0.511050003 | None | None | N |
| C/H | 0.3592 | ambiguous | 0.4604 | ambiguous | -1.925 | Destabilizing | 0.356 | N | 0.599 | neutral | None | None | None | None | N |
| C/I | 0.5695 | likely_pathogenic | 0.6602 | pathogenic | -0.46 | Destabilizing | 0.356 | N | 0.616 | neutral | None | None | None | None | N |
| C/K | 0.2807 | likely_benign | 0.3718 | ambiguous | -0.728 | Destabilizing | None | N | 0.456 | neutral | None | None | None | None | N |
| C/L | 0.359 | ambiguous | 0.4319 | ambiguous | -0.46 | Destabilizing | 0.031 | N | 0.534 | neutral | None | None | None | None | N |
| C/M | 0.4867 | ambiguous | 0.5513 | ambiguous | -0.179 | Destabilizing | 0.356 | N | 0.576 | neutral | None | None | None | None | N |
| C/N | 0.5401 | ambiguous | 0.6283 | pathogenic | -1.36 | Destabilizing | 0.072 | N | 0.597 | neutral | None | None | None | None | N |
| C/P | 0.987 | likely_pathogenic | 0.9912 | pathogenic | -0.749 | Destabilizing | 0.356 | N | 0.631 | neutral | None | None | None | None | N |
| C/Q | 0.2421 | likely_benign | 0.3181 | benign | -0.841 | Destabilizing | 0.001 | N | 0.448 | neutral | None | None | None | None | N |
| C/R | 0.1223 | likely_benign | 0.1577 | benign | -1.296 | Destabilizing | None | N | 0.441 | neutral | N | 0.455282744 | None | None | N |
| C/S | 0.3476 | ambiguous | 0.4322 | ambiguous | -1.602 | Destabilizing | 0.002 | N | 0.388 | neutral | N | 0.473980424 | None | None | N |
| C/T | 0.4748 | ambiguous | 0.5688 | pathogenic | -1.179 | Destabilizing | 0.038 | N | 0.553 | neutral | None | None | None | None | N |
| C/V | 0.4507 | ambiguous | 0.5211 | ambiguous | -0.749 | Destabilizing | 0.072 | N | 0.553 | neutral | None | None | None | None | N |
| C/W | 0.5811 | likely_pathogenic | 0.6812 | pathogenic | -1.268 | Destabilizing | 0.924 | D | 0.571 | neutral | N | 0.467666776 | None | None | N |
| C/Y | 0.3356 | likely_benign | 0.4116 | ambiguous | -1.01 | Destabilizing | 0.295 | N | 0.579 | neutral | N | 0.469338665 | 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.