Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13700 | 41323;41324;41325 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| N2AB | 12059 | 36400;36401;36402 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| N2A | 11132 | 33619;33620;33621 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| N2B | 4635 | 14128;14129;14130 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| Novex-1 | 4760 | 14503;14504;14505 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| Novex-2 | 4827 | 14704;14705;14706 | chr2:178636629;178636628;178636627 | chr2:179501356;179501355;179501354 |
| 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 | rs1438452689  |
-0.624 | 0.104 | N | 0.403 | 0.17 | 0.37762505005 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1438452689 |
-0.624 | 0.104 | N | 0.403 | 0.17 | 0.37762505005 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 3.2774E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1438452689 |
-0.624 | 0.104 | N | 0.403 | 0.17 | 0.37762505005 | gnomAD-4.0.0 | 7.43819E-06 | None | None | None | None | I | None | 1.33522E-05 | 1.0006E-04 | None | 0 | 0 | None | 0 | 0 | 2.5433E-06 | 1.09789E-05 | 1.60174E-05 |
| V/I | rs748716483 |
-0.15 | 0.002 | N | 0.169 | 0.026 | 0.107399877778 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.35E-05 | 0 |
| V/I | rs748716483 |
-0.15 | 0.002 | N | 0.169 | 0.026 | 0.107399877778 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs748716483 |
-0.15 | 0.002 | N | 0.169 | 0.026 | 0.107399877778 | gnomAD-4.0.0 | 9.29791E-06 | None | None | None | None | I | None | 0 | 3.33545E-05 | None | 0 | 0 | None | 0 | 0 | 7.62989E-06 | 3.29402E-05 | 1.60185E-05 |
| V/L | None | None | 0.022 | N | 0.377 | 0.022 | 0.162503812791 | gnomAD-4.0.0 | 3.42182E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49806E-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 | 0.1397 | likely_benign | 0.1969 | benign | -0.633 | Destabilizing | 0.104 | N | 0.403 | neutral | N | 0.443132746 | None | None | I |
| V/C | 0.8204 | likely_pathogenic | 0.8614 | pathogenic | -0.765 | Destabilizing | 0.968 | D | 0.493 | neutral | None | None | None | None | I |
| V/D | 0.4634 | ambiguous | 0.5774 | pathogenic | 0.172 | Stabilizing | 0.667 | D | 0.686 | prob.neutral | N | 0.456801486 | None | None | I |
| V/E | 0.3653 | ambiguous | 0.4657 | ambiguous | 0.093 | Stabilizing | 0.726 | D | 0.624 | neutral | None | None | None | None | I |
| V/F | 0.2219 | likely_benign | 0.2865 | benign | -0.738 | Destabilizing | 0.715 | D | 0.463 | neutral | N | 0.495447226 | None | None | I |
| V/G | 0.1995 | likely_benign | 0.271 | benign | -0.808 | Destabilizing | 0.667 | D | 0.679 | prob.neutral | N | 0.496680763 | None | None | I |
| V/H | 0.659 | likely_pathogenic | 0.737 | pathogenic | -0.378 | Destabilizing | 0.968 | D | 0.702 | prob.neutral | None | None | None | None | I |
| V/I | 0.0838 | likely_benign | 0.0881 | benign | -0.313 | Destabilizing | 0.002 | N | 0.169 | neutral | N | 0.42816147 | None | None | I |
| V/K | 0.4843 | ambiguous | 0.5852 | pathogenic | -0.337 | Destabilizing | 0.726 | D | 0.629 | neutral | None | None | None | None | I |
| V/L | 0.2034 | likely_benign | 0.2628 | benign | -0.313 | Destabilizing | 0.022 | N | 0.377 | neutral | N | 0.443990628 | None | None | I |
| V/M | 0.2041 | likely_benign | 0.2386 | benign | -0.356 | Destabilizing | 0.567 | D | 0.418 | neutral | None | None | None | None | I |
| V/N | 0.3546 | ambiguous | 0.4675 | ambiguous | -0.135 | Destabilizing | 0.89 | D | 0.692 | prob.neutral | None | None | None | None | I |
| V/P | 0.3085 | likely_benign | 0.4422 | ambiguous | -0.384 | Destabilizing | 0.89 | D | 0.629 | neutral | None | None | None | None | I |
| V/Q | 0.3807 | ambiguous | 0.4617 | ambiguous | -0.315 | Destabilizing | 0.89 | D | 0.636 | neutral | None | None | None | None | I |
| V/R | 0.4053 | ambiguous | 0.5027 | ambiguous | 0.067 | Stabilizing | 0.726 | D | 0.684 | prob.neutral | None | None | None | None | I |
| V/S | 0.1928 | likely_benign | 0.2657 | benign | -0.647 | Destabilizing | 0.726 | D | 0.549 | neutral | None | None | None | None | I |
| V/T | 0.1607 | likely_benign | 0.2108 | benign | -0.61 | Destabilizing | 0.272 | N | 0.413 | neutral | None | None | None | None | I |
| V/W | 0.8663 | likely_pathogenic | 0.9118 | pathogenic | -0.808 | Destabilizing | 0.968 | D | 0.717 | prob.delet. | None | None | None | None | I |
| V/Y | 0.6621 | likely_pathogenic | 0.7673 | pathogenic | -0.491 | Destabilizing | 0.726 | D | 0.452 | neutral | None | None | None | None | I |
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.