Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17458 | 52597;52598;52599 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| N2AB | 15817 | 47674;47675;47676 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| N2A | 14890 | 44893;44894;44895 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| N2B | 8393 | 25402;25403;25404 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| Novex-1 | 8518 | 25777;25778;25779 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| Novex-2 | 8585 | 25978;25979;25980 | chr2:178608639;178608638;178608637 | chr2:179473366;179473365;179473364 |
| 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 | rs760430370  |
-1.41 | 0.435 | N | 0.467 | 0.224 | None | gnomAD-2.1.1 | 1.81E-05 | None | None | None | None | N | None | 0 | 2.86E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.17E-05 | 0 |
| V/A | rs760430370 |
-1.41 | 0.435 | N | 0.467 | 0.224 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/A | rs760430370 |
-1.41 | 0.435 | N | 0.467 | 0.224 | None | gnomAD-4.0.0 | 3.47506E-05 | None | None | None | None | N | None | 1.33658E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.41104E-05 | 0 | 4.81062E-05 |
| V/I | rs763928739 |
-0.282 | 0.01 | N | 0.248 | 0.069 | 0.308904156042 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| V/I | rs763928739 |
-0.282 | 0.01 | N | 0.248 | 0.069 | 0.308904156042 | gnomAD-4.0.0 | 4.78947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.59594E-06 | 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 | 0.2626 | likely_benign | 0.2621 | benign | -1.202 | Destabilizing | 0.435 | N | 0.467 | neutral | N | 0.43136961 | None | None | N |
| V/C | 0.6926 | likely_pathogenic | 0.6693 | pathogenic | -0.637 | Destabilizing | 0.995 | D | 0.445 | neutral | None | None | None | None | N |
| V/D | 0.3536 | ambiguous | 0.3465 | ambiguous | -0.512 | Destabilizing | 0.93 | D | 0.649 | prob.neutral | N | 0.417133664 | None | None | N |
| V/E | 0.2246 | likely_benign | 0.2255 | benign | -0.426 | Destabilizing | 0.897 | D | 0.564 | neutral | None | None | None | None | N |
| V/F | 0.1629 | likely_benign | 0.1606 | benign | -0.713 | Destabilizing | 0.868 | D | 0.465 | neutral | N | 0.49709317 | None | None | N |
| V/G | 0.4198 | ambiguous | 0.4044 | ambiguous | -1.573 | Destabilizing | 0.93 | D | 0.631 | neutral | N | 0.461039156 | None | None | N |
| V/H | 0.5654 | likely_pathogenic | 0.5429 | ambiguous | -0.919 | Destabilizing | 0.995 | D | 0.65 | prob.neutral | None | None | None | None | N |
| V/I | 0.0677 | likely_benign | 0.0663 | benign | -0.256 | Destabilizing | 0.01 | N | 0.248 | neutral | N | 0.421229975 | None | None | N |
| V/K | 0.443 | ambiguous | 0.4251 | ambiguous | -0.689 | Destabilizing | 0.032 | N | 0.492 | neutral | None | None | None | None | N |
| V/L | 0.149 | likely_benign | 0.1472 | benign | -0.256 | Destabilizing | 0.002 | N | 0.339 | neutral | N | 0.438354298 | None | None | N |
| V/M | 0.1562 | likely_benign | 0.1485 | benign | -0.296 | Destabilizing | 0.897 | D | 0.41 | neutral | None | None | None | None | N |
| V/N | 0.2818 | likely_benign | 0.2704 | benign | -0.659 | Destabilizing | 0.946 | D | 0.655 | prob.neutral | None | None | None | None | N |
| V/P | 0.5445 | ambiguous | 0.5514 | ambiguous | -0.538 | Destabilizing | 0.982 | D | 0.623 | neutral | None | None | None | None | N |
| V/Q | 0.3461 | ambiguous | 0.3285 | benign | -0.652 | Destabilizing | 0.897 | D | 0.617 | neutral | None | None | None | None | N |
| V/R | 0.4203 | ambiguous | 0.4065 | ambiguous | -0.416 | Destabilizing | 0.813 | D | 0.647 | neutral | None | None | None | None | N |
| V/S | 0.2693 | likely_benign | 0.2573 | benign | -1.301 | Destabilizing | 0.712 | D | 0.545 | neutral | None | None | None | None | N |
| V/T | 0.1984 | likely_benign | 0.1907 | benign | -1.079 | Destabilizing | 0.834 | D | 0.368 | neutral | None | None | None | None | N |
| V/W | 0.7951 | likely_pathogenic | 0.7821 | pathogenic | -0.939 | Destabilizing | 0.995 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/Y | 0.4616 | ambiguous | 0.4625 | ambiguous | -0.579 | Destabilizing | 0.946 | D | 0.453 | 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.