Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15671 | 47236;47237;47238 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| N2AB | 14030 | 42313;42314;42315 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| N2A | 13103 | 39532;39533;39534 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| N2B | 6606 | 20041;20042;20043 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| Novex-1 | 6731 | 20416;20417;20418 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| Novex-2 | 6798 | 20617;20618;20619 | chr2:178618447;178618446;178618445 | chr2:179483174;179483173;179483172 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs748275289  |
-0.925 | 1.0 | N | 0.733 | 0.402 | 0.347438807231 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs748275289 |
-0.622 | 1.0 | N | 0.72 | 0.317 | 0.302793454619 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| D/N | rs748275289 |
-0.622 | 1.0 | N | 0.72 | 0.317 | 0.302793454619 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| D/N | rs748275289 |
-0.622 | 1.0 | N | 0.72 | 0.317 | 0.302793454619 | gnomAD-4.0.0 | 4.96162E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.78619E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6296 | likely_pathogenic | 0.4868 | ambiguous | -0.624 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.463453537 | None | None | N |
| D/C | 0.9446 | likely_pathogenic | 0.8675 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/E | 0.4545 | ambiguous | 0.4039 | ambiguous | -0.441 | Destabilizing | 1.0 | D | 0.457 | neutral | N | 0.47482703 | None | None | N |
| D/F | 0.9484 | likely_pathogenic | 0.8874 | pathogenic | -0.632 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| D/G | 0.6361 | likely_pathogenic | 0.4919 | ambiguous | -0.841 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | N | 0.480802682 | None | None | N |
| D/H | 0.844 | likely_pathogenic | 0.6962 | pathogenic | -0.764 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.501167317 | None | None | N |
| D/I | 0.9363 | likely_pathogenic | 0.8649 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/K | 0.9442 | likely_pathogenic | 0.8618 | pathogenic | 0.112 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/L | 0.8596 | likely_pathogenic | 0.7501 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/M | 0.9567 | likely_pathogenic | 0.9166 | pathogenic | 0.321 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/N | 0.3672 | ambiguous | 0.274 | benign | -0.174 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.477671558 | None | None | N |
| D/P | 0.9431 | likely_pathogenic | 0.8724 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| D/Q | 0.8485 | likely_pathogenic | 0.7173 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/R | 0.9136 | likely_pathogenic | 0.7998 | pathogenic | 0.141 | Stabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| D/S | 0.437 | ambiguous | 0.3209 | benign | -0.312 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| D/T | 0.8104 | likely_pathogenic | 0.6922 | pathogenic | -0.139 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| D/V | 0.8463 | likely_pathogenic | 0.7196 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.651048029 | None | None | N |
| D/W | 0.9864 | likely_pathogenic | 0.9618 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/Y | 0.7943 | likely_pathogenic | 0.6309 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.746 | deleterious | D | 0.651406108 | 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.