Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32735 | 98428;98429;98430 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| N2AB | 31094 | 93505;93506;93507 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| N2A | 30167 | 90724;90725;90726 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| N2B | 23670 | 71233;71234;71235 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| Novex-1 | 23795 | 71608;71609;71610 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| Novex-2 | 23862 | 71809;71810;71811 | chr2:178539862;178539861;178539860 | chr2:179404589;179404588;179404587 |
| 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/V | rs761246331  |
-0.802 | None | N | 0.185 | 0.065 | None | gnomAD-2.1.1 | 3.92E-05 | None | None | None | None | I | None | 2.47954E-04 | 1.41443E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs761246331 |
-0.802 | None | N | 0.185 | 0.065 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | I | None | 3.13797E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs761246331 |
-0.802 | None | N | 0.185 | 0.065 | None | gnomAD-4.0.0 | 1.92108E-05 | None | None | None | None | I | None | 2.93725E-04 | 1.0002E-04 | None | 0 | 0 | None | 0 | 0 | 8.4763E-07 | 0 | 3.20195E-05 |
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 | 0.1623 | likely_benign | 0.1453 | benign | -0.723 | Destabilizing | 0.035 | N | 0.321 | neutral | None | None | None | None | I |
| I/C | 0.5803 | likely_pathogenic | 0.516 | ambiguous | -0.425 | Destabilizing | 0.824 | D | 0.355 | neutral | None | None | None | None | I |
| I/D | 0.4399 | ambiguous | 0.3926 | ambiguous | -0.636 | Destabilizing | 0.555 | D | 0.41 | neutral | None | None | None | None | I |
| I/E | 0.3561 | ambiguous | 0.3039 | benign | -0.735 | Destabilizing | 0.555 | D | 0.4 | neutral | None | None | None | None | I |
| I/F | 0.1512 | likely_benign | 0.1448 | benign | -0.77 | Destabilizing | 0.38 | N | 0.337 | neutral | None | None | None | None | I |
| I/G | 0.4301 | ambiguous | 0.3863 | ambiguous | -0.898 | Destabilizing | 0.262 | N | 0.389 | neutral | None | None | None | None | I |
| I/H | 0.3262 | likely_benign | 0.2761 | benign | -0.287 | Destabilizing | 0.935 | D | 0.439 | neutral | None | None | None | None | I |
| I/K | 0.2685 | likely_benign | 0.2111 | benign | -0.504 | Destabilizing | 0.317 | N | 0.403 | neutral | N | 0.380732933 | None | None | I |
| I/L | 0.0968 | likely_benign | 0.0893 | benign | -0.378 | Destabilizing | 0.012 | N | 0.245 | neutral | N | 0.438666516 | None | None | I |
| I/M | 0.1028 | likely_benign | 0.0991 | benign | -0.327 | Destabilizing | 0.317 | N | 0.385 | neutral | N | 0.466218477 | None | None | I |
| I/N | 0.1356 | likely_benign | 0.1189 | benign | -0.172 | Destabilizing | 0.555 | D | 0.421 | neutral | None | None | None | None | I |
| I/P | 0.828 | likely_pathogenic | 0.8062 | pathogenic | -0.46 | Destabilizing | 0.791 | D | 0.431 | neutral | None | None | None | None | I |
| I/Q | 0.2745 | likely_benign | 0.2322 | benign | -0.445 | Destabilizing | 0.791 | D | 0.443 | neutral | None | None | None | None | I |
| I/R | 0.2315 | likely_benign | 0.1853 | benign | 0.103 | Stabilizing | 0.484 | N | 0.445 | neutral | N | 0.401878996 | None | None | I |
| I/S | 0.1465 | likely_benign | 0.1247 | benign | -0.538 | Destabilizing | 0.081 | N | 0.344 | neutral | None | None | None | None | I |
| I/T | 0.1133 | likely_benign | 0.1049 | benign | -0.538 | Destabilizing | 0.001 | N | 0.203 | neutral | N | 0.354413124 | None | None | I |
| I/V | 0.0619 | likely_benign | 0.0657 | benign | -0.46 | Destabilizing | None | N | 0.185 | neutral | N | 0.408516967 | None | None | I |
| I/W | 0.7735 | likely_pathogenic | 0.7599 | pathogenic | -0.808 | Destabilizing | 0.935 | D | 0.492 | neutral | None | None | None | None | I |
| I/Y | 0.4443 | ambiguous | 0.4078 | ambiguous | -0.564 | Destabilizing | 0.555 | D | 0.367 | neutral | None | None | 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.