Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29773 | 89542;89543;89544 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| N2AB | 28132 | 84619;84620;84621 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| N2A | 27205 | 81838;81839;81840 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| N2B | 20708 | 62347;62348;62349 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| Novex-1 | 20833 | 62722;62723;62724 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| Novex-2 | 20900 | 62923;62924;62925 | chr2:178553688;178553687;178553686 | chr2:179418415;179418414;179418413 |
| 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 | rs77853750  |
-0.24 | None | N | 0.122 | 0.076 | 0.471941563831 | gnomAD-2.1.1 | 3.29385E-03 | None | None | None | None | N | None | 3.45896E-02 | 1.75419E-03 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-05 | 1.82533E-03 |
| I/L | rs77853750 |
-0.24 | None | N | 0.122 | 0.076 | 0.471941563831 | gnomAD-3.1.2 | 1.01061E-02 | None | None | None | None | N | None | 3.44287E-02 | 5.04191E-03 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 1.46998E-04 | 0 | 1.05062E-02 |
| I/L | rs77853750 |
-0.24 | None | N | 0.122 | 0.076 | 0.471941563831 | 1000 genomes | 1.05831E-02 | None | None | None | None | N | None | 3.78E-02 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/L | rs77853750 |
-0.24 | None | N | 0.122 | 0.076 | 0.471941563831 | gnomAD-4.0.0 | 6.84197E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 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 | 0.3071 | likely_benign | 0.2312 | benign | -2.008 | Highly Destabilizing | None | N | 0.306 | neutral | None | None | None | None | N |
| I/C | 0.477 | ambiguous | 0.4185 | ambiguous | -0.988 | Destabilizing | 0.051 | N | 0.613 | neutral | None | None | None | None | N |
| I/D | 0.793 | likely_pathogenic | 0.7373 | pathogenic | -2.569 | Highly Destabilizing | None | N | 0.574 | neutral | None | None | None | None | N |
| I/E | 0.4877 | ambiguous | 0.389 | ambiguous | -2.259 | Highly Destabilizing | None | N | 0.512 | neutral | None | None | None | None | N |
| I/F | 0.1357 | likely_benign | 0.1302 | benign | -1.195 | Destabilizing | 0.002 | N | 0.334 | neutral | None | None | None | None | N |
| I/G | 0.6084 | likely_pathogenic | 0.5038 | ambiguous | -2.604 | Highly Destabilizing | None | N | 0.52 | neutral | None | None | None | None | N |
| I/H | 0.4254 | ambiguous | 0.3471 | ambiguous | -2.407 | Highly Destabilizing | 0.008 | N | 0.65 | neutral | None | None | None | None | N |
| I/K | 0.196 | likely_benign | 0.1417 | benign | -1.304 | Destabilizing | None | N | 0.478 | neutral | N | 0.361039947 | None | None | N |
| I/L | 0.0836 | likely_benign | 0.0769 | benign | -0.244 | Destabilizing | None | N | 0.122 | neutral | N | 0.427262152 | None | None | N |
| I/M | 0.051 | likely_benign | 0.0415 | benign | -0.257 | Destabilizing | None | N | 0.127 | neutral | N | 0.413450279 | None | None | N |
| I/N | 0.3293 | likely_benign | 0.2882 | benign | -1.959 | Destabilizing | None | N | 0.591 | neutral | None | None | None | None | N |
| I/P | 0.98 | likely_pathogenic | 0.9729 | pathogenic | -0.819 | Destabilizing | 0.001 | N | 0.613 | neutral | None | None | None | None | N |
| I/Q | 0.2631 | likely_benign | 0.1844 | benign | -1.612 | Destabilizing | None | N | 0.481 | neutral | None | None | None | None | N |
| I/R | 0.195 | likely_benign | 0.1403 | benign | -1.485 | Destabilizing | None | N | 0.557 | neutral | N | 0.412026127 | None | None | N |
| I/S | 0.249 | likely_benign | 0.2003 | benign | -2.529 | Highly Destabilizing | None | N | 0.427 | neutral | None | None | None | None | N |
| I/T | 0.2018 | likely_benign | 0.1686 | benign | -2.054 | Highly Destabilizing | None | N | 0.35 | neutral | N | 0.444983908 | None | None | N |
| I/V | 0.0864 | likely_benign | 0.0744 | benign | -0.819 | Destabilizing | None | N | 0.119 | neutral | N | 0.435169559 | None | None | N |
| I/W | 0.6369 | likely_pathogenic | 0.5572 | ambiguous | -1.663 | Destabilizing | 0.116 | N | 0.699 | prob.neutral | None | None | None | None | N |
| I/Y | 0.2992 | likely_benign | 0.2796 | benign | -1.283 | Destabilizing | 0.003 | N | 0.483 | 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.