Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19270 | 58033;58034;58035 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| N2AB | 17629 | 53110;53111;53112 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| N2A | 16702 | 50329;50330;50331 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| N2B | 10205 | 30838;30839;30840 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| Novex-1 | 10330 | 31213;31214;31215 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| Novex-2 | 10397 | 31414;31415;31416 | chr2:178595546;178595545;178595544 | chr2:179460273;179460272;179460271 |
| 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/I | None | None | None | N | 0.167 | 0.029 | 0.141422826196 | gnomAD-4.0.0 | 7.06833E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.20503E-07 | 0 | 0 |
| V/L | rs369440319  |
-0.473 | 0.004 | N | 0.487 | 0.11 | None | gnomAD-2.1.1 | 1.74287E-04 | None | None | None | None | N | None | 1.75312E-03 | 1.08015E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs369440319 |
-0.473 | 0.004 | N | 0.487 | 0.11 | None | gnomAD-3.1.2 | 4.48117E-04 | None | None | None | None | N | None | 1.6222E-03 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs369440319 |
-0.473 | 0.004 | N | 0.487 | 0.11 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/L | rs369440319 |
-0.473 | 0.004 | N | 0.487 | 0.11 | None | gnomAD-4.0.0 | 7.7236E-05 | None | None | None | None | N | None | 1.53E-03 | 7.53693E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.58393E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1128 | likely_benign | 0.1262 | benign | -1.27 | Destabilizing | 0.012 | N | 0.594 | neutral | N | 0.43337726 | None | None | N |
| V/C | 0.4815 | ambiguous | 0.5227 | ambiguous | -0.755 | Destabilizing | 0.685 | D | 0.611 | neutral | None | None | None | None | N |
| V/D | 0.3976 | ambiguous | 0.4793 | ambiguous | -1.232 | Destabilizing | 0.177 | N | 0.742 | deleterious | N | 0.503199918 | None | None | N |
| V/E | 0.2236 | likely_benign | 0.2742 | benign | -1.1 | Destabilizing | 0.221 | N | 0.677 | prob.neutral | None | None | None | None | N |
| V/F | 0.1728 | likely_benign | 0.2037 | benign | -0.676 | Destabilizing | 0.177 | N | 0.691 | prob.delet. | N | 0.484787516 | None | None | N |
| V/G | 0.2416 | likely_benign | 0.2675 | benign | -1.696 | Destabilizing | 0.058 | N | 0.739 | deleterious | N | 0.448538714 | None | None | N |
| V/H | 0.3575 | ambiguous | 0.4196 | ambiguous | -1.23 | Destabilizing | 0.869 | D | 0.775 | deleterious | None | None | None | None | N |
| V/I | 0.0779 | likely_benign | 0.0793 | benign | -0.15 | Destabilizing | None | N | 0.167 | neutral | N | 0.417370445 | None | None | N |
| V/K | 0.2057 | likely_benign | 0.2619 | benign | -1.024 | Destabilizing | 0.221 | N | 0.676 | prob.neutral | None | None | None | None | N |
| V/L | 0.1635 | likely_benign | 0.1829 | benign | -0.15 | Destabilizing | 0.004 | N | 0.487 | neutral | N | 0.384161948 | None | None | N |
| V/M | 0.1184 | likely_benign | 0.1262 | benign | -0.18 | Destabilizing | 0.221 | N | 0.555 | neutral | None | None | None | None | N |
| V/N | 0.2515 | likely_benign | 0.2914 | benign | -1.147 | Destabilizing | 0.221 | N | 0.753 | deleterious | None | None | None | None | N |
| V/P | 0.8757 | likely_pathogenic | 0.9002 | pathogenic | -0.49 | Destabilizing | 0.366 | N | 0.666 | prob.neutral | None | None | None | None | N |
| V/Q | 0.1819 | likely_benign | 0.2073 | benign | -1.1 | Destabilizing | 0.366 | N | 0.676 | prob.neutral | None | None | None | None | N |
| V/R | 0.1604 | likely_benign | 0.2023 | benign | -0.771 | Destabilizing | 0.221 | N | 0.748 | deleterious | None | None | None | None | N |
| V/S | 0.1419 | likely_benign | 0.1646 | benign | -1.729 | Destabilizing | 0.039 | N | 0.666 | prob.neutral | None | None | None | None | N |
| V/T | 0.0912 | likely_benign | 0.0981 | benign | -1.465 | Destabilizing | None | N | 0.231 | neutral | None | None | None | None | N |
| V/W | 0.7003 | likely_pathogenic | 0.7472 | pathogenic | -1.055 | Destabilizing | 0.869 | D | 0.801 | deleterious | None | None | None | None | N |
| V/Y | 0.4572 | ambiguous | 0.5096 | ambiguous | -0.628 | Destabilizing | 0.366 | N | 0.663 | prob.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.