Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22021 | 66286;66287;66288 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| N2AB | 20380 | 61363;61364;61365 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| N2A | 19453 | 58582;58583;58584 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| N2B | 12956 | 39091;39092;39093 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| Novex-1 | 13081 | 39466;39467;39468 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| Novex-2 | 13148 | 39667;39668;39669 | chr2:178582395;178582394;178582393 | chr2:179447122;179447121;179447120 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1423136139  |
None | 0.003 | N | 0.121 | 0.207 | 0.243398259712 | 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 |
| I/L | rs1423136139 |
None | 0.003 | N | 0.121 | 0.207 | 0.243398259712 | gnomAD-4.0.0 | 1.86014E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54377E-06 | 0 | 0 |
| I/M | None | None | 0.901 | N | 0.509 | 0.27 | 0.290222751274 | gnomAD-4.0.0 | 4.10746E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.8006E-05 | 1.65782E-05 |
| I/T | rs774090305 |
-1.238 | 0.722 | N | 0.505 | 0.351 | 0.469415673434 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs774090305 |
-1.238 | 0.722 | N | 0.505 | 0.351 | 0.469415673434 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs774090305 |
-1.238 | 0.722 | N | 0.505 | 0.351 | 0.469415673434 | gnomAD-4.0.0 | 6.5786E-06 | None | None | None | None | N | None | 2.41523E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8384 | likely_pathogenic | 0.8424 | pathogenic | -1.506 | Destabilizing | 0.775 | D | 0.419 | neutral | None | None | None | None | N |
| I/C | 0.978 | likely_pathogenic | 0.9807 | pathogenic | -0.746 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | N |
| I/D | 0.9926 | likely_pathogenic | 0.9918 | pathogenic | -0.873 | Destabilizing | 0.987 | D | 0.667 | neutral | None | None | None | None | N |
| I/E | 0.959 | likely_pathogenic | 0.9601 | pathogenic | -0.869 | Destabilizing | 0.961 | D | 0.673 | neutral | None | None | None | None | N |
| I/F | 0.6264 | likely_pathogenic | 0.6639 | pathogenic | -1.07 | Destabilizing | 0.858 | D | 0.485 | neutral | None | None | None | None | N |
| I/G | 0.9794 | likely_pathogenic | 0.9783 | pathogenic | -1.815 | Destabilizing | 0.961 | D | 0.672 | neutral | None | None | None | None | N |
| I/H | 0.9554 | likely_pathogenic | 0.9549 | pathogenic | -0.897 | Destabilizing | 0.996 | D | 0.674 | neutral | None | None | None | None | N |
| I/K | 0.9039 | likely_pathogenic | 0.9141 | pathogenic | -0.896 | Destabilizing | 0.949 | D | 0.673 | neutral | N | 0.472570367 | None | None | N |
| I/L | 0.2274 | likely_benign | 0.2715 | benign | -0.736 | Destabilizing | 0.003 | N | 0.121 | neutral | N | 0.492446994 | None | None | N |
| I/M | 0.2432 | likely_benign | 0.2699 | benign | -0.559 | Destabilizing | 0.901 | D | 0.509 | neutral | N | 0.486092451 | None | None | N |
| I/N | 0.9362 | likely_pathogenic | 0.9305 | pathogenic | -0.716 | Destabilizing | 0.987 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/P | 0.98 | likely_pathogenic | 0.9753 | pathogenic | -0.962 | Destabilizing | 0.987 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8898 | likely_pathogenic | 0.886 | pathogenic | -0.882 | Destabilizing | 0.987 | D | 0.666 | neutral | None | None | None | None | N |
| I/R | 0.8225 | likely_pathogenic | 0.8242 | pathogenic | -0.293 | Destabilizing | 0.949 | D | 0.676 | prob.neutral | N | 0.517187936 | None | None | N |
| I/S | 0.8947 | likely_pathogenic | 0.8859 | pathogenic | -1.304 | Destabilizing | 0.961 | D | 0.564 | neutral | None | None | None | None | N |
| I/T | 0.7 | likely_pathogenic | 0.7188 | pathogenic | -1.179 | Destabilizing | 0.722 | D | 0.505 | neutral | N | 0.472359723 | None | None | N |
| I/V | 0.3511 | ambiguous | 0.4013 | ambiguous | -0.962 | Destabilizing | 0.19 | N | 0.309 | neutral | N | 0.502759988 | None | None | N |
| I/W | 0.9431 | likely_pathogenic | 0.9455 | pathogenic | -1.125 | Destabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/Y | 0.9224 | likely_pathogenic | 0.9225 | pathogenic | -0.899 | Destabilizing | 0.961 | D | 0.567 | 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.