Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31864 | 95815;95816;95817 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| N2AB | 30223 | 90892;90893;90894 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| N2A | 29296 | 88111;88112;88113 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| N2B | 22799 | 68620;68621;68622 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| Novex-1 | 22924 | 68995;68996;68997 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| Novex-2 | 22991 | 69196;69197;69198 | chr2:178545520;178545519;178545518 | chr2:179410247;179410246;179410245 |
| 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 | None | None | 1.0 | N | 0.799 | 0.552 | 0.581377893825 | gnomAD-4.0.0 | 5.47409E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59822E-06 | 3.47826E-05 | 1.65684E-05 |
| Y/F | None | None | 0.999 | N | 0.575 | 0.42 | 0.417081434665 | gnomAD-4.0.0 | 6.84261E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99556E-07 | 0 | 0 |
| Y/H | None | None | 1.0 | N | 0.733 | 0.462 | 0.417208245017 | gnomAD-4.0.0 | 3.18308E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85914E-06 | 0 | 3.0248E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.3976 | ambiguous | 0.4162 | ambiguous | -1.007 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| Y/C | 0.1308 | likely_benign | 0.1322 | benign | -0.119 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.5068218 | None | None | N |
| Y/D | 0.3218 | likely_benign | 0.3413 | ambiguous | 0.547 | Stabilizing | 1.0 | D | 0.787 | deleterious | N | 0.446002628 | None | None | N |
| Y/E | 0.5814 | likely_pathogenic | 0.6134 | pathogenic | 0.554 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/F | 0.1224 | likely_benign | 0.1202 | benign | -0.411 | Destabilizing | 0.999 | D | 0.575 | neutral | N | 0.466071256 | None | None | N |
| Y/G | 0.3014 | likely_benign | 0.3201 | benign | -1.223 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| Y/H | 0.1908 | likely_benign | 0.2032 | benign | 0.07 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.44696542 | None | None | N |
| Y/I | 0.5345 | ambiguous | 0.5361 | ambiguous | -0.428 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| Y/K | 0.4548 | ambiguous | 0.4998 | ambiguous | -0.146 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/L | 0.4062 | ambiguous | 0.4072 | ambiguous | -0.428 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| Y/M | 0.5713 | likely_pathogenic | 0.5675 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| Y/N | 0.1647 | likely_benign | 0.1794 | benign | -0.435 | Destabilizing | 1.0 | D | 0.794 | deleterious | N | 0.414506285 | None | None | N |
| Y/P | 0.5173 | ambiguous | 0.5467 | ambiguous | -0.605 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/Q | 0.3917 | ambiguous | 0.4262 | ambiguous | -0.363 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| Y/R | 0.2925 | likely_benign | 0.3355 | benign | 0.157 | Stabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| Y/S | 0.1547 | likely_benign | 0.1676 | benign | -0.853 | Destabilizing | 1.0 | D | 0.778 | deleterious | N | 0.38020171 | None | None | N |
| Y/T | 0.2727 | likely_benign | 0.2999 | benign | -0.756 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| Y/V | 0.3955 | ambiguous | 0.3982 | ambiguous | -0.605 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| Y/W | 0.4007 | ambiguous | 0.3948 | ambiguous | -0.408 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | 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.