Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25249 | 75970;75971;75972 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| N2AB | 23608 | 71047;71048;71049 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| N2A | 22681 | 68266;68267;68268 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| N2B | 16184 | 48775;48776;48777 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| Novex-1 | 16309 | 49150;49151;49152 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| Novex-2 | 16376 | 49351;49352;49353 | chr2:178570387;178570386;178570385 | chr2:179435114;179435113;179435112 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs397517702  |
-0.358 | 1.0 | N | 0.729 | 0.441 | 0.580315741719 | gnomAD-2.1.1 | 8.2561E-04 | None | None | None | None | I | None | 0 | 5.81E-05 | None | 0 | 0 | None | 6.54365E-03 | None | 0 | 1.79E-05 | 0 |
| R/C | rs397517702 |
-0.358 | 1.0 | N | 0.729 | 0.441 | 0.580315741719 | gnomAD-3.1.2 | 1.77613E-04 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 4.97306E-03 | 4.79846E-04 |
| R/C | rs397517702 |
-0.358 | 1.0 | N | 0.729 | 0.441 | 0.580315741719 | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 6.1E-03 | None |
| R/C | rs397517702 |
-0.358 | 1.0 | N | 0.729 | 0.441 | 0.580315741719 | gnomAD-4.0.0 | 4.0232E-04 | None | None | None | None | I | None | 1.33362E-05 | 3.33589E-05 | None | 0 | 0 | None | 0 | 6.60502E-04 | 5.08656E-06 | 6.86285E-03 | 1.76175E-04 |
| R/H | rs773286477 |
-1.08 | 1.0 | N | 0.687 | 0.346 | 0.325263233342 | gnomAD-2.1.1 | 4.45E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-05 | 1.66945E-04 |
| R/H | rs773286477 |
-1.08 | 1.0 | N | 0.687 | 0.346 | 0.325263233342 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs773286477 |
-1.08 | 1.0 | N | 0.687 | 0.346 | 0.325263233342 | gnomAD-4.0.0 | 3.40965E-05 | None | None | None | None | I | None | 1.33558E-05 | 5.00534E-05 | None | 0 | 6.70991E-05 | None | 0 | 0 | 3.39099E-05 | 3.29388E-05 | 8.01025E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9767 | likely_pathogenic | 0.9842 | pathogenic | -0.568 | Destabilizing | 0.999 | D | 0.481 | neutral | None | None | None | None | I |
| R/C | 0.7085 | likely_pathogenic | 0.7442 | pathogenic | -0.579 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.513604456 | None | None | I |
| R/D | 0.9937 | likely_pathogenic | 0.9951 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| R/E | 0.9679 | likely_pathogenic | 0.9775 | pathogenic | 0.156 | Stabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | I |
| R/F | 0.9755 | likely_pathogenic | 0.9842 | pathogenic | -0.632 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| R/G | 0.9428 | likely_pathogenic | 0.9617 | pathogenic | -0.817 | Destabilizing | 1.0 | D | 0.515 | neutral | N | 0.509453887 | None | None | I |
| R/H | 0.2925 | likely_benign | 0.4127 | ambiguous | -1.165 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.466493713 | None | None | I |
| R/I | 0.9698 | likely_pathogenic | 0.9795 | pathogenic | 0.075 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/K | 0.5929 | likely_pathogenic | 0.6513 | pathogenic | -0.543 | Destabilizing | 0.998 | D | 0.429 | neutral | None | None | None | None | I |
| R/L | 0.8997 | likely_pathogenic | 0.9275 | pathogenic | 0.075 | Stabilizing | 1.0 | D | 0.515 | neutral | N | 0.487484803 | None | None | I |
| R/M | 0.9593 | likely_pathogenic | 0.9759 | pathogenic | -0.242 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| R/N | 0.9762 | likely_pathogenic | 0.9838 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| R/P | 0.9916 | likely_pathogenic | 0.994 | pathogenic | -0.119 | Destabilizing | 1.0 | D | 0.619 | neutral | N | 0.482066753 | None | None | I |
| R/Q | 0.5916 | likely_pathogenic | 0.6987 | pathogenic | -0.276 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| R/S | 0.9731 | likely_pathogenic | 0.9815 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.576 | neutral | N | 0.484307513 | None | None | I |
| R/T | 0.9703 | likely_pathogenic | 0.9817 | pathogenic | -0.513 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | I |
| R/V | 0.9728 | likely_pathogenic | 0.9806 | pathogenic | -0.119 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| R/W | 0.75 | likely_pathogenic | 0.8267 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| R/Y | 0.9177 | likely_pathogenic | 0.9447 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.659 | 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.