Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20548 | 61867;61868;61869 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| N2AB | 18907 | 56944;56945;56946 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| N2A | 17980 | 54163;54164;54165 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| N2B | 11483 | 34672;34673;34674 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| Novex-1 | 11608 | 35047;35048;35049 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| Novex-2 | 11675 | 35248;35249;35250 | chr2:178590083;178590082;178590081 | chr2:179454810;179454809;179454808 |
| 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/T | None | None | 0.022 | N | 0.339 | 0.147 | 0.378322506985 | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52564E-05 | None | 0 | 0 | 0 | 0 | 1.65706E-05 |
| I/V | None | None | 0.022 | N | 0.185 | 0.041 | 0.315609569513 | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86028E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3568 | ambiguous | 0.3179 | benign | -1.858 | Destabilizing | 0.525 | D | 0.513 | neutral | None | None | None | None | N |
| I/C | 0.6001 | likely_pathogenic | 0.5949 | pathogenic | -1.529 | Destabilizing | 0.998 | D | 0.59 | neutral | None | None | None | None | N |
| I/D | 0.7232 | likely_pathogenic | 0.7235 | pathogenic | -1.154 | Destabilizing | 0.949 | D | 0.617 | neutral | None | None | None | None | N |
| I/E | 0.5819 | likely_pathogenic | 0.5853 | pathogenic | -1.081 | Destabilizing | 0.949 | D | 0.612 | neutral | None | None | None | None | N |
| I/F | 0.1908 | likely_benign | 0.1704 | benign | -1.248 | Destabilizing | 0.934 | D | 0.569 | neutral | N | 0.493379995 | None | None | N |
| I/G | 0.6661 | likely_pathogenic | 0.638 | pathogenic | -2.238 | Highly Destabilizing | 0.842 | D | 0.592 | neutral | None | None | None | None | N |
| I/H | 0.4403 | ambiguous | 0.432 | ambiguous | -1.438 | Destabilizing | 0.998 | D | 0.65 | neutral | None | None | None | None | N |
| I/K | 0.4724 | ambiguous | 0.5054 | ambiguous | -1.073 | Destabilizing | 0.842 | D | 0.617 | neutral | None | None | None | None | N |
| I/L | 0.125 | likely_benign | 0.1243 | benign | -0.851 | Destabilizing | 0.005 | N | 0.221 | neutral | N | 0.456861835 | None | None | N |
| I/M | 0.1064 | likely_benign | 0.1019 | benign | -0.926 | Destabilizing | 0.934 | D | 0.559 | neutral | N | 0.462134369 | None | None | N |
| I/N | 0.2435 | likely_benign | 0.2337 | benign | -1.014 | Destabilizing | 0.934 | D | 0.607 | neutral | N | 0.46481992 | None | None | N |
| I/P | 0.9828 | likely_pathogenic | 0.9863 | pathogenic | -1.159 | Destabilizing | 0.974 | D | 0.611 | neutral | None | None | None | None | N |
| I/Q | 0.4294 | ambiguous | 0.414 | ambiguous | -1.124 | Destabilizing | 0.974 | D | 0.62 | neutral | None | None | None | None | N |
| I/R | 0.3674 | ambiguous | 0.4165 | ambiguous | -0.664 | Destabilizing | 0.974 | D | 0.612 | neutral | None | None | None | None | N |
| I/S | 0.2487 | likely_benign | 0.2344 | benign | -1.799 | Destabilizing | 0.669 | D | 0.538 | neutral | N | 0.423037263 | None | None | N |
| I/T | 0.1762 | likely_benign | 0.1497 | benign | -1.597 | Destabilizing | 0.022 | N | 0.339 | neutral | N | 0.37143222 | None | None | N |
| I/V | 0.079 | likely_benign | 0.0716 | benign | -1.159 | Destabilizing | 0.022 | N | 0.185 | neutral | N | 0.407934524 | None | None | N |
| I/W | 0.811 | likely_pathogenic | 0.7877 | pathogenic | -1.307 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | N |
| I/Y | 0.4708 | ambiguous | 0.4852 | ambiguous | -1.049 | Destabilizing | 0.974 | D | 0.581 | 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.