Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| N2AB | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| N2A | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| N2B | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| Novex-1 | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| Novex-2 | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
| Novex-3 | 45 | 358;359;360 | chr2:178802300;178802299;178802298 | chr2:179667027;179667026;179667025 |
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/L | rs142028110  |
-0.047 | 0.002 | N | 0.529 | 0.202 | 0.417460480802 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | -0.635(TCAP) | N | None | 2.80336E-04 | 2.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs142028110 |
-0.047 | 0.002 | N | 0.529 | 0.202 | 0.417460480802 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | -0.635(TCAP) | N | None | 1.68952E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs142028110 |
-0.047 | 0.002 | N | 0.529 | 0.202 | 0.417460480802 | gnomAD-4.0.0 | 6.84074E-07 | None | None | None | -0.635(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 0 | 0 |
| V/M | None | None | 0.404 | N | 0.544 | 0.197 | 0.517377062552 | gnomAD-4.0.0 | 6.84074E-07 | None | None | None | -0.362(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.082 | likely_benign | 0.0928 | benign | -0.775 | Destabilizing | None | N | 0.151 | neutral | N | 0.495113797 | None | -0.397(TCAP) | N |
| V/C | 0.8744 | likely_pathogenic | 0.9102 | pathogenic | -0.681 | Destabilizing | 0.719 | D | 0.63 | neutral | None | None | None | -0.367(TCAP) | N |
| V/D | 0.2381 | likely_benign | 0.3559 | ambiguous | -0.002 | Destabilizing | 0.292 | N | 0.572 | neutral | None | None | None | -0.367(TCAP) | N |
| V/E | 0.1521 | likely_benign | 0.2052 | benign | -0.053 | Destabilizing | None | N | 0.357 | neutral | N | 0.391956929 | None | -0.461(TCAP) | N |
| V/F | 0.2258 | likely_benign | 0.2873 | benign | -0.663 | Destabilizing | 0.557 | D | 0.621 | neutral | None | None | None | -0.49(TCAP) | N |
| V/G | 0.1572 | likely_benign | 0.1999 | benign | -0.999 | Destabilizing | 0.107 | N | 0.58 | neutral | N | 0.510234567 | None | -0.323(TCAP) | N |
| V/H | 0.539 | ambiguous | 0.6596 | pathogenic | -0.484 | Destabilizing | 0.772 | D | 0.7 | prob.neutral | None | None | None | 0.313(TCAP) | N |
| V/I | 0.0951 | likely_benign | 0.1068 | benign | -0.306 | Destabilizing | 0.015 | N | 0.487 | neutral | None | None | None | -0.635(TCAP) | N |
| V/K | 0.2377 | likely_benign | 0.3321 | benign | -0.531 | Destabilizing | 0.04 | N | 0.553 | neutral | None | None | None | -0.513(TCAP) | N |
| V/L | 0.1763 | likely_benign | 0.1525 | benign | -0.306 | Destabilizing | 0.002 | N | 0.529 | neutral | N | 0.447871277 | None | -0.635(TCAP) | N |
| V/M | 0.1428 | likely_benign | 0.168 | benign | -0.373 | Destabilizing | 0.404 | N | 0.544 | neutral | N | 0.508717162 | None | -0.362(TCAP) | N |
| V/N | 0.1711 | likely_benign | 0.2358 | benign | -0.337 | Destabilizing | 0.041 | N | 0.699 | prob.neutral | None | None | None | -0.545(TCAP) | N |
| V/P | 0.1783 | likely_benign | 0.2289 | benign | -0.425 | Destabilizing | 0.041 | N | 0.67 | neutral | None | None | None | -0.554(TCAP) | N |
| V/Q | 0.217 | likely_benign | 0.2827 | benign | -0.488 | Destabilizing | 0.094 | N | 0.677 | prob.neutral | None | None | None | -0.546(TCAP) | N |
| V/R | 0.2464 | likely_benign | 0.3461 | ambiguous | -0.107 | Destabilizing | 0.383 | N | 0.695 | prob.neutral | None | None | None | -0.35(TCAP) | N |
| V/S | 0.13 | likely_benign | 0.1648 | benign | -0.855 | Destabilizing | 0.046 | N | 0.559 | neutral | None | None | None | -0.252(TCAP) | N |
| V/T | 0.1348 | likely_benign | 0.1643 | benign | -0.791 | Destabilizing | 0.019 | N | 0.442 | neutral | None | None | None | -0.362(TCAP) | N |
| V/W | 0.8491 | likely_pathogenic | 0.9116 | pathogenic | -0.778 | Destabilizing | 0.975 | D | 0.737 | prob.delet. | None | None | None | -0.667(TCAP) | N |
| V/Y | 0.5835 | likely_pathogenic | 0.6878 | pathogenic | -0.469 | Destabilizing | 0.557 | D | 0.622 | neutral | None | None | None | -0.518(TCAP) | 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.