Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15948 | 48067;48068;48069 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| N2AB | 14307 | 43144;43145;43146 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| N2A | 13380 | 40363;40364;40365 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| N2B | 6883 | 20872;20873;20874 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| Novex-1 | 7008 | 21247;21248;21249 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| Novex-2 | 7075 | 21448;21449;21450 | chr2:178617153;178617152;178617151 | chr2:179481880;179481879;179481878 |
| 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/S | rs767552822  |
-1.458 | 0.003 | N | 0.592 | 0.138 | 0.52437609879 | gnomAD-2.1.1 | 4.18E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.29E-06 | 0 |
| I/S | rs767552822 |
-1.458 | 0.003 | N | 0.592 | 0.138 | 0.52437609879 | gnomAD-4.0.0 | 1.60645E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88118E-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 | 0.3474 | ambiguous | 0.3325 | benign | -1.422 | Destabilizing | None | N | 0.471 | neutral | None | None | None | None | N |
| I/C | 0.6356 | likely_pathogenic | 0.6303 | pathogenic | -0.872 | Destabilizing | 0.703 | D | 0.576 | neutral | None | None | None | None | N |
| I/D | 0.624 | likely_pathogenic | 0.5911 | pathogenic | -0.499 | Destabilizing | 0.25 | N | 0.72 | deleterious | None | None | None | None | N |
| I/E | 0.4894 | ambiguous | 0.4794 | ambiguous | -0.418 | Destabilizing | 0.143 | N | 0.671 | prob.neutral | None | None | None | None | N |
| I/F | 0.2105 | likely_benign | 0.1965 | benign | -0.753 | Destabilizing | 0.468 | N | 0.547 | neutral | N | 0.457383612 | None | None | N |
| I/G | 0.656 | likely_pathogenic | 0.6234 | pathogenic | -1.794 | Destabilizing | 0.064 | N | 0.658 | prob.neutral | None | None | None | None | N |
| I/H | 0.5205 | ambiguous | 0.4815 | ambiguous | -0.85 | Destabilizing | 0.703 | D | 0.721 | deleterious | None | None | None | None | N |
| I/K | 0.3332 | likely_benign | 0.3089 | benign | -0.805 | Destabilizing | 0.143 | N | 0.661 | prob.neutral | None | None | None | None | N |
| I/L | 0.1338 | likely_benign | 0.1248 | benign | -0.451 | Destabilizing | None | N | 0.183 | neutral | N | 0.443185248 | None | None | N |
| I/M | 0.1224 | likely_benign | 0.1149 | benign | -0.497 | Destabilizing | 0.468 | N | 0.495 | neutral | N | 0.455645457 | None | None | N |
| I/N | 0.2337 | likely_benign | 0.2055 | benign | -0.841 | Destabilizing | 0.201 | N | 0.776 | deleterious | N | 0.456190829 | None | None | N |
| I/P | 0.4807 | ambiguous | 0.5493 | ambiguous | -0.744 | Destabilizing | 0.403 | N | 0.786 | deleterious | None | None | None | None | N |
| I/Q | 0.399 | ambiguous | 0.3699 | ambiguous | -0.854 | Destabilizing | 0.013 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/R | 0.3193 | likely_benign | 0.3153 | benign | -0.405 | Destabilizing | 0.25 | N | 0.782 | deleterious | None | None | None | None | N |
| I/S | 0.2856 | likely_benign | 0.2576 | benign | -1.544 | Destabilizing | 0.003 | N | 0.592 | neutral | N | 0.435551155 | None | None | N |
| I/T | 0.2879 | likely_benign | 0.2549 | benign | -1.326 | Destabilizing | 0.003 | N | 0.474 | neutral | N | 0.443487868 | None | None | N |
| I/V | 0.1015 | likely_benign | 0.1034 | benign | -0.744 | Destabilizing | None | N | 0.127 | neutral | N | 0.425606793 | None | None | N |
| I/W | 0.7913 | likely_pathogenic | 0.7847 | pathogenic | -0.864 | Destabilizing | 0.964 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Y | 0.4449 | ambiguous | 0.4351 | ambiguous | -0.594 | Destabilizing | 0.703 | D | 0.703 | 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.