Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24319 | 73180;73181;73182 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| N2AB | 22678 | 68257;68258;68259 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| N2A | 21751 | 65476;65477;65478 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| N2B | 15254 | 45985;45986;45987 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| Novex-1 | 15379 | 46360;46361;46362 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| Novex-2 | 15446 | 46561;46562;46563 | chr2:178573177;178573176;178573175 | chr2:179437904;179437903;179437902 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | N | 0.783 | 0.421 | 0.374434639691 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs1241907204  |
0.35 | 1.0 | N | 0.785 | 0.355 | 0.414281671643 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1241907204 |
0.35 | 1.0 | N | 0.785 | 0.355 | 0.414281671643 | gnomAD-4.0.0 | 1.597E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78118E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7107 | likely_pathogenic | 0.638 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.722 | deleterious | N | 0.478799341 | None | None | N |
| D/C | 0.9614 | likely_pathogenic | 0.9397 | pathogenic | 0.225 | Stabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| D/E | 0.5778 | likely_pathogenic | 0.5074 | ambiguous | -0.342 | Destabilizing | 0.999 | D | 0.466 | neutral | N | 0.486278744 | None | None | N |
| D/F | 0.9655 | likely_pathogenic | 0.9445 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| D/G | 0.7484 | likely_pathogenic | 0.6676 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.486548022 | None | None | N |
| D/H | 0.8503 | likely_pathogenic | 0.7988 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.889 | deleterious | N | 0.495043945 | None | None | N |
| D/I | 0.9118 | likely_pathogenic | 0.8796 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| D/K | 0.9129 | likely_pathogenic | 0.8908 | pathogenic | 0.364 | Stabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| D/L | 0.8924 | likely_pathogenic | 0.8533 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/M | 0.9647 | likely_pathogenic | 0.9507 | pathogenic | 0.346 | Stabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| D/N | 0.2789 | likely_benign | 0.2439 | benign | 0.239 | Stabilizing | 1.0 | D | 0.785 | deleterious | N | 0.486548022 | None | None | N |
| D/P | 0.9265 | likely_pathogenic | 0.9026 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| D/Q | 0.8686 | likely_pathogenic | 0.8419 | pathogenic | 0.225 | Stabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| D/R | 0.9039 | likely_pathogenic | 0.8802 | pathogenic | 0.423 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| D/S | 0.4999 | ambiguous | 0.4314 | ambiguous | 0.131 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/T | 0.811 | likely_pathogenic | 0.7659 | pathogenic | 0.24 | Stabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| D/V | 0.8057 | likely_pathogenic | 0.7492 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.754 | deleterious | N | 0.514198156 | None | None | N |
| D/W | 0.993 | likely_pathogenic | 0.9898 | pathogenic | -0.397 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/Y | 0.7973 | likely_pathogenic | 0.7172 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.510692664 | 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.