Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2614 | 8065;8066;8067 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| N2AB | 2614 | 8065;8066;8067 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| N2A | 2614 | 8065;8066;8067 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| N2B | 2568 | 7927;7928;7929 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| Novex-1 | 2568 | 7927;7928;7929 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| Novex-2 | 2568 | 7927;7928;7929 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
| Novex-3 | 2614 | 8065;8066;8067 | chr2:178773124;178773123;178773122 | chr2:179637851;179637850;179637849 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs535026241  |
-0.744 | 0.175 | N | 0.399 | 0.075 | 0.112648838833 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| K/N | rs535026241 |
-0.744 | 0.175 | N | 0.399 | 0.075 | 0.112648838833 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92308E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs535026241 |
-0.744 | 0.175 | N | 0.399 | 0.075 | 0.112648838833 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| K/N | rs535026241 |
-0.744 | 0.175 | N | 0.399 | 0.075 | 0.112648838833 | gnomAD-4.0.0 | 6.56478E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92753E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2873 | likely_benign | 0.3162 | benign | -0.404 | Destabilizing | 0.104 | N | 0.342 | neutral | None | None | None | None | N |
| K/C | 0.571 | likely_pathogenic | 0.5992 | pathogenic | -0.512 | Destabilizing | 0.958 | D | 0.524 | neutral | None | None | None | None | N |
| K/D | 0.3638 | ambiguous | 0.3675 | ambiguous | 0.205 | Stabilizing | 0.124 | N | 0.444 | neutral | None | None | None | None | N |
| K/E | 0.1209 | likely_benign | 0.1206 | benign | 0.276 | Stabilizing | 0.003 | N | 0.187 | neutral | N | 0.444868925 | None | None | N |
| K/F | 0.4811 | ambiguous | 0.5009 | ambiguous | -0.314 | Destabilizing | 0.497 | N | 0.531 | neutral | None | None | None | None | N |
| K/G | 0.4871 | ambiguous | 0.511 | ambiguous | -0.714 | Destabilizing | 0.22 | N | 0.448 | neutral | None | None | None | None | N |
| K/H | 0.2046 | likely_benign | 0.2134 | benign | -1.041 | Destabilizing | 0.667 | D | 0.5 | neutral | None | None | None | None | N |
| K/I | 0.1461 | likely_benign | 0.1515 | benign | 0.367 | Stabilizing | 0.096 | N | 0.455 | neutral | N | 0.507018696 | None | None | N |
| K/L | 0.1919 | likely_benign | 0.2073 | benign | 0.367 | Stabilizing | 0.055 | N | 0.377 | neutral | None | None | None | None | N |
| K/M | 0.1141 | likely_benign | 0.1168 | benign | 0.272 | Stabilizing | 0.025 | N | 0.296 | neutral | None | None | None | None | N |
| K/N | 0.1922 | likely_benign | 0.1888 | benign | -0.103 | Destabilizing | 0.175 | N | 0.399 | neutral | N | 0.444868925 | None | None | N |
| K/P | 0.8527 | likely_pathogenic | 0.8552 | pathogenic | 0.14 | Stabilizing | 0.364 | N | 0.527 | neutral | None | None | None | None | N |
| K/Q | 0.1125 | likely_benign | 0.1146 | benign | -0.267 | Destabilizing | 0.008 | N | 0.277 | neutral | N | 0.449503296 | None | None | N |
| K/R | 0.0963 | likely_benign | 0.0976 | benign | -0.304 | Destabilizing | 0.001 | N | 0.267 | neutral | N | 0.448340014 | None | None | N |
| K/S | 0.2661 | likely_benign | 0.2785 | benign | -0.812 | Destabilizing | 0.055 | N | 0.413 | neutral | None | None | None | None | N |
| K/T | 0.1012 | likely_benign | 0.1058 | benign | -0.547 | Destabilizing | 0.003 | N | 0.251 | neutral | N | 0.440563572 | None | None | N |
| K/V | 0.1703 | likely_benign | 0.1812 | benign | 0.14 | Stabilizing | 0.004 | N | 0.373 | neutral | None | None | None | None | N |
| K/W | 0.6202 | likely_pathogenic | 0.6297 | pathogenic | -0.165 | Destabilizing | 0.958 | D | 0.559 | neutral | None | None | None | None | N |
| K/Y | 0.3814 | ambiguous | 0.3951 | ambiguous | 0.152 | Stabilizing | 0.859 | D | 0.526 | 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.