Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20785 | 62578;62579;62580 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| N2AB | 19144 | 57655;57656;57657 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| N2A | 18217 | 54874;54875;54876 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| N2B | 11720 | 35383;35384;35385 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| Novex-1 | 11845 | 35758;35759;35760 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| Novex-2 | 11912 | 35959;35960;35961 | chr2:178589372;178589371;178589370 | chr2:179454099;179454098;179454097 |
| 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/E | rs766020138  |
-0.531 | 0.001 | N | 0.157 | 0.069 | 0.0138822411134 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/E | rs766020138 |
-0.531 | 0.001 | N | 0.157 | 0.069 | 0.0138822411134 | gnomAD-4.0.0 | 2.73738E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59826E-06 | 0 | 0 |
| D/Y | None | None | 0.957 | N | 0.573 | 0.345 | 0.446310458034 | gnomAD-4.0.0 | 6.8434E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99557E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3344 | likely_benign | 0.3698 | ambiguous | -0.355 | Destabilizing | 0.338 | N | 0.403 | neutral | N | 0.437028067 | None | None | I |
| D/C | 0.8334 | likely_pathogenic | 0.8619 | pathogenic | 0.131 | Stabilizing | 0.991 | D | 0.658 | neutral | None | None | None | None | I |
| D/E | 0.1445 | likely_benign | 0.142 | benign | -0.372 | Destabilizing | 0.001 | N | 0.157 | neutral | N | 0.392906357 | None | None | I |
| D/F | 0.8721 | likely_pathogenic | 0.8937 | pathogenic | -0.351 | Destabilizing | 0.967 | D | 0.575 | neutral | None | None | None | None | I |
| D/G | 0.3707 | ambiguous | 0.4211 | ambiguous | -0.567 | Destabilizing | 0.505 | D | 0.334 | neutral | N | 0.428445869 | None | None | I |
| D/H | 0.5958 | likely_pathogenic | 0.6739 | pathogenic | -0.378 | Destabilizing | 0.879 | D | 0.403 | neutral | N | 0.461790439 | None | None | I |
| D/I | 0.7375 | likely_pathogenic | 0.779 | pathogenic | 0.158 | Stabilizing | 0.906 | D | 0.577 | neutral | None | None | None | None | I |
| D/K | 0.6433 | likely_pathogenic | 0.7022 | pathogenic | 0.329 | Stabilizing | 0.018 | N | 0.216 | neutral | None | None | None | None | I |
| D/L | 0.7245 | likely_pathogenic | 0.7737 | pathogenic | 0.158 | Stabilizing | 0.826 | D | 0.5 | neutral | None | None | None | None | I |
| D/M | 0.7832 | likely_pathogenic | 0.824 | pathogenic | 0.433 | Stabilizing | 0.991 | D | 0.573 | neutral | None | None | None | None | I |
| D/N | 0.1747 | likely_benign | 0.2002 | benign | 0.011 | Stabilizing | 0.505 | D | 0.421 | neutral | N | 0.44152981 | None | None | I |
| D/P | 0.9837 | likely_pathogenic | 0.9857 | pathogenic | 0.009 | Stabilizing | 0.906 | D | 0.367 | neutral | None | None | None | None | I |
| D/Q | 0.4556 | ambiguous | 0.5181 | ambiguous | 0.042 | Stabilizing | 0.404 | N | 0.369 | neutral | None | None | None | None | I |
| D/R | 0.7536 | likely_pathogenic | 0.7924 | pathogenic | 0.386 | Stabilizing | 0.704 | D | 0.445 | neutral | None | None | None | None | I |
| D/S | 0.2165 | likely_benign | 0.2517 | benign | -0.093 | Destabilizing | 0.404 | N | 0.331 | neutral | None | None | None | None | I |
| D/T | 0.4217 | ambiguous | 0.4726 | ambiguous | 0.074 | Stabilizing | 0.575 | D | 0.375 | neutral | None | None | None | None | I |
| D/V | 0.5281 | ambiguous | 0.5747 | pathogenic | 0.009 | Stabilizing | 0.782 | D | 0.5 | neutral | N | 0.495172294 | None | None | I |
| D/W | 0.9731 | likely_pathogenic | 0.9789 | pathogenic | -0.224 | Destabilizing | 0.991 | D | 0.68 | prob.neutral | None | None | None | None | I |
| D/Y | 0.5559 | ambiguous | 0.6171 | pathogenic | -0.112 | Destabilizing | 0.957 | D | 0.573 | neutral | N | 0.50092483 | None | None | I |
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.