Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21217 | 63874;63875;63876 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| N2AB | 19576 | 58951;58952;58953 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| N2A | 18649 | 56170;56171;56172 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| N2B | 12152 | 36679;36680;36681 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| Novex-1 | 12277 | 37054;37055;37056 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| Novex-2 | 12344 | 37255;37256;37257 | chr2:178587660;178587659;178587658 | chr2:179452387;179452386;179452385 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1351844757  |
-0.647 | 0.003 | N | 0.195 | 0.175 | 0.374613414588 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14969E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1351844757 |
-0.647 | 0.003 | N | 0.195 | 0.175 | 0.374613414588 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1351844757 |
-0.647 | 0.003 | N | 0.195 | 0.175 | 0.374613414588 | gnomAD-4.0.0 | 3.84796E-06 | None | None | None | None | N | None | 5.08199E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1214985099 |
-0.235 | 0.001 | N | 0.147 | 0.127 | 0.378322506985 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs1214985099 |
-0.235 | 0.001 | N | 0.147 | 0.127 | 0.378322506985 | gnomAD-4.0.0 | 1.5932E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3233 | likely_benign | 0.3432 | ambiguous | -0.413 | Destabilizing | 0.003 | N | 0.195 | neutral | N | 0.453691896 | None | None | N |
| V/C | 0.7763 | likely_pathogenic | 0.8188 | pathogenic | -0.655 | Destabilizing | 0.973 | D | 0.482 | neutral | None | None | None | None | N |
| V/D | 0.596 | likely_pathogenic | 0.5888 | pathogenic | -0.215 | Destabilizing | 0.879 | D | 0.566 | neutral | N | 0.487516469 | None | None | N |
| V/E | 0.4513 | ambiguous | 0.4441 | ambiguous | -0.315 | Destabilizing | 0.826 | D | 0.471 | neutral | None | None | None | None | N |
| V/F | 0.2437 | likely_benign | 0.2759 | benign | -0.585 | Destabilizing | 0.782 | D | 0.444 | neutral | D | 0.523573269 | None | None | N |
| V/G | 0.3471 | ambiguous | 0.3592 | ambiguous | -0.557 | Destabilizing | 0.338 | N | 0.482 | neutral | N | 0.502043204 | None | None | N |
| V/H | 0.7116 | likely_pathogenic | 0.7443 | pathogenic | -0.167 | Destabilizing | 0.991 | D | 0.605 | neutral | None | None | None | None | N |
| V/I | 0.0756 | likely_benign | 0.0822 | benign | -0.178 | Destabilizing | 0.001 | N | 0.147 | neutral | N | 0.474741959 | None | None | N |
| V/K | 0.5186 | ambiguous | 0.5499 | ambiguous | -0.462 | Destabilizing | 0.826 | D | 0.479 | neutral | None | None | None | None | N |
| V/L | 0.1774 | likely_benign | 0.2038 | benign | -0.178 | Destabilizing | 0.031 | N | 0.284 | neutral | N | 0.462178094 | None | None | N |
| V/M | 0.2026 | likely_benign | 0.2242 | benign | -0.351 | Destabilizing | 0.826 | D | 0.437 | neutral | None | None | None | None | N |
| V/N | 0.4378 | ambiguous | 0.4703 | ambiguous | -0.206 | Destabilizing | 0.906 | D | 0.589 | neutral | None | None | None | None | N |
| V/P | 0.5365 | ambiguous | 0.5567 | ambiguous | -0.221 | Destabilizing | 0.906 | D | 0.531 | neutral | None | None | None | None | N |
| V/Q | 0.4433 | ambiguous | 0.469 | ambiguous | -0.408 | Destabilizing | 0.906 | D | 0.554 | neutral | None | None | None | None | N |
| V/R | 0.4808 | ambiguous | 0.5049 | ambiguous | -0.003 | Destabilizing | 0.906 | D | 0.589 | neutral | None | None | None | None | N |
| V/S | 0.365 | ambiguous | 0.3786 | ambiguous | -0.573 | Destabilizing | 0.404 | N | 0.428 | neutral | None | None | None | None | N |
| V/T | 0.3349 | likely_benign | 0.3544 | ambiguous | -0.568 | Destabilizing | 0.575 | D | 0.339 | neutral | None | None | None | None | N |
| V/W | 0.8541 | likely_pathogenic | 0.8802 | pathogenic | -0.689 | Destabilizing | 0.991 | D | 0.655 | neutral | None | None | None | None | N |
| V/Y | 0.651 | likely_pathogenic | 0.6904 | pathogenic | -0.385 | Destabilizing | 0.906 | D | 0.466 | 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.