Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32774 | 98545;98546;98547 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| N2AB | 31133 | 93622;93623;93624 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| N2A | 30206 | 90841;90842;90843 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| N2B | 23709 | 71350;71351;71352 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| Novex-1 | 23834 | 71725;71726;71727 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| Novex-2 | 23901 | 71926;71927;71928 | chr2:178539745;178539744;178539743 | chr2:179404472;179404471;179404470 |
| 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/E | rs767435784  |
-0.555 | 1.0 | N | 0.477 | 0.173 | 0.183819452728 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/E | rs767435784 |
-0.555 | 1.0 | N | 0.477 | 0.173 | 0.183819452728 | gnomAD-4.0.0 | 1.5912E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02352E-05 |
| D/V | None | None | 1.0 | N | 0.874 | 0.378 | 0.369495900351 | gnomAD-4.0.0 | 1.59119E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85819E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4878 | ambiguous | 0.5701 | pathogenic | -0.724 | Destabilizing | 1.0 | D | 0.789 | deleterious | N | 0.455995043 | None | None | N |
| D/C | 0.87 | likely_pathogenic | 0.8961 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| D/E | 0.4499 | ambiguous | 0.5241 | ambiguous | -0.586 | Destabilizing | 1.0 | D | 0.477 | neutral | N | 0.394042507 | None | None | N |
| D/F | 0.8389 | likely_pathogenic | 0.8738 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| D/G | 0.5879 | likely_pathogenic | 0.6602 | pathogenic | -1.155 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.461979653 | None | None | N |
| D/H | 0.5601 | ambiguous | 0.6273 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.824 | deleterious | N | 0.48631795 | None | None | N |
| D/I | 0.7138 | likely_pathogenic | 0.7562 | pathogenic | 0.464 | Stabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| D/K | 0.7585 | likely_pathogenic | 0.8301 | pathogenic | -0.616 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| D/L | 0.6903 | likely_pathogenic | 0.7544 | pathogenic | 0.464 | Stabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| D/M | 0.862 | likely_pathogenic | 0.8909 | pathogenic | 1.105 | Stabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| D/N | 0.2203 | likely_benign | 0.2601 | benign | -1.037 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.456688476 | None | None | N |
| D/P | 0.9889 | likely_pathogenic | 0.9917 | pathogenic | 0.091 | Stabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| D/Q | 0.7129 | likely_pathogenic | 0.7741 | pathogenic | -0.696 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/R | 0.7782 | likely_pathogenic | 0.8349 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| D/S | 0.3116 | likely_benign | 0.3637 | ambiguous | -1.598 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/T | 0.5444 | ambiguous | 0.6001 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| D/V | 0.5446 | ambiguous | 0.6012 | pathogenic | 0.091 | Stabilizing | 1.0 | D | 0.874 | deleterious | N | 0.412108193 | None | None | N |
| D/W | 0.9726 | likely_pathogenic | 0.9773 | pathogenic | -0.608 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| D/Y | 0.4676 | ambiguous | 0.5165 | ambiguous | -0.306 | Destabilizing | 1.0 | D | 0.871 | deleterious | N | 0.466865398 | 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.