Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33703 | 101332;101333;101334 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| N2AB | 32062 | 96409;96410;96411 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| N2A | 31135 | 93628;93629;93630 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| N2B | 24638 | 74137;74138;74139 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| Novex-1 | 24763 | 74512;74513;74514 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| Novex-2 | 24830 | 74713;74714;74715 | chr2:178535508;178535507;178535506 | chr2:179400235;179400234;179400233 |
| 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/L | rs576025689  |
None | 1.0 | N | 0.667 | 0.416 | 0.519187973786 | gnomAD-4.0.0 | 1.3684E-06 | None | None | None | None | N | None | 2.98793E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| R/Q | rs576025689 |
-0.538 | 1.0 | N | 0.737 | 0.251 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 1.29182E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.88E-06 | 0 |
| R/Q | rs576025689 |
-0.538 | 1.0 | N | 0.737 | 0.251 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07125E-04 | 0 |
| R/Q | rs576025689 |
-0.538 | 1.0 | N | 0.737 | 0.251 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/Q | rs576025689 |
-0.538 | 1.0 | N | 0.737 | 0.251 | None | gnomAD-4.0.0 | 1.42517E-05 | None | None | None | None | N | None | 5.33134E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.0171E-05 | 6.58776E-05 | 1.60056E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9286 | likely_pathogenic | 0.8377 | pathogenic | -0.834 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.8377 | likely_pathogenic | 0.6757 | pathogenic | -0.751 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/D | 0.9847 | likely_pathogenic | 0.9651 | pathogenic | -0.373 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/E | 0.9203 | likely_pathogenic | 0.8579 | pathogenic | -0.335 | Destabilizing | 0.997 | D | 0.634 | neutral | None | None | None | None | N |
| R/F | 0.9796 | likely_pathogenic | 0.953 | pathogenic | -1.243 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/G | 0.8722 | likely_pathogenic | 0.7299 | pathogenic | -1.012 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.44144217 | None | None | N |
| R/H | 0.6615 | likely_pathogenic | 0.4879 | ambiguous | -1.31 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/I | 0.9301 | likely_pathogenic | 0.8418 | pathogenic | -0.388 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| R/K | 0.3634 | ambiguous | 0.2593 | benign | -0.781 | Destabilizing | 0.979 | D | 0.457 | neutral | None | None | None | None | N |
| R/L | 0.8961 | likely_pathogenic | 0.7839 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.468557628 | None | None | N |
| R/M | 0.9329 | likely_pathogenic | 0.8375 | pathogenic | -0.311 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/N | 0.9735 | likely_pathogenic | 0.9359 | pathogenic | -0.184 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/P | 0.9475 | likely_pathogenic | 0.8916 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.466068469 | None | None | N |
| R/Q | 0.5309 | ambiguous | 0.3777 | ambiguous | -0.587 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.482982149 | None | None | N |
| R/S | 0.9554 | likely_pathogenic | 0.8977 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| R/T | 0.9211 | likely_pathogenic | 0.8159 | pathogenic | -0.725 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/V | 0.9433 | likely_pathogenic | 0.8771 | pathogenic | -0.519 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/W | 0.8152 | likely_pathogenic | 0.6754 | pathogenic | -1.044 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/Y | 0.953 | likely_pathogenic | 0.9002 | pathogenic | -0.668 | Destabilizing | 0.999 | D | 0.743 | deleterious | 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.