Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27575 | 82948;82949;82950 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| N2AB | 25934 | 78025;78026;78027 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| N2A | 25007 | 75244;75245;75246 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| N2B | 18510 | 55753;55754;55755 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| Novex-1 | 18635 | 56128;56129;56130 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| Novex-2 | 18702 | 56329;56330;56331 | chr2:178563409;178563408;178563407 | chr2:179428136;179428135;179428134 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs763068189  |
-0.789 | 0.334 | N | 0.428 | 0.154 | 0.230578612272 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs763068189 |
-0.789 | 0.334 | N | 0.428 | 0.154 | 0.230578612272 | gnomAD-4.0.0 | 3.18304E-06 | None | None | None | None | N | None | 0 | 2.28718E-05 | None | 0 | 0 | None | 0 | 0 | 2.85845E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0932 | likely_benign | 0.0983 | benign | -0.575 | Destabilizing | 0.25 | N | 0.39 | neutral | None | None | None | None | N |
| S/C | 0.0941 | likely_benign | 0.0968 | benign | -0.488 | Destabilizing | 0.99 | D | 0.525 | neutral | N | 0.476461347 | None | None | N |
| S/D | 0.7145 | likely_pathogenic | 0.7158 | pathogenic | -0.717 | Destabilizing | 0.447 | N | 0.427 | neutral | None | None | None | None | N |
| S/E | 0.8078 | likely_pathogenic | 0.7866 | pathogenic | -0.697 | Destabilizing | 0.617 | D | 0.445 | neutral | None | None | None | None | N |
| S/F | 0.3597 | ambiguous | 0.3394 | benign | -0.694 | Destabilizing | 0.85 | D | 0.635 | neutral | None | None | None | None | N |
| S/G | 0.0732 | likely_benign | 0.0822 | benign | -0.85 | Destabilizing | 0.334 | N | 0.428 | neutral | N | 0.42306984 | None | None | N |
| S/H | 0.4931 | ambiguous | 0.4783 | ambiguous | -1.477 | Destabilizing | 0.92 | D | 0.541 | neutral | None | None | None | None | N |
| S/I | 0.1819 | likely_benign | 0.1914 | benign | 0.053 | Stabilizing | 0.004 | N | 0.434 | neutral | N | 0.513326485 | None | None | N |
| S/K | 0.8672 | likely_pathogenic | 0.852 | pathogenic | -0.85 | Destabilizing | 0.617 | D | 0.459 | neutral | None | None | None | None | N |
| S/L | 0.1544 | likely_benign | 0.1441 | benign | 0.053 | Stabilizing | 0.103 | N | 0.521 | neutral | None | None | None | None | N |
| S/M | 0.2293 | likely_benign | 0.2369 | benign | 0.287 | Stabilizing | 0.85 | D | 0.542 | neutral | None | None | None | None | N |
| S/N | 0.144 | likely_benign | 0.162 | benign | -0.917 | Destabilizing | 0.007 | N | 0.127 | neutral | N | 0.44007952 | None | None | N |
| S/P | 0.6824 | likely_pathogenic | 0.6753 | pathogenic | -0.121 | Destabilizing | 0.92 | D | 0.557 | neutral | None | None | None | None | N |
| S/Q | 0.6359 | likely_pathogenic | 0.6142 | pathogenic | -1.009 | Destabilizing | 0.92 | D | 0.513 | neutral | None | None | None | None | N |
| S/R | 0.8085 | likely_pathogenic | 0.7814 | pathogenic | -0.828 | Destabilizing | 0.81 | D | 0.557 | neutral | N | 0.470861 | None | None | N |
| S/T | 0.1029 | likely_benign | 0.1017 | benign | -0.793 | Destabilizing | 0.002 | N | 0.145 | neutral | N | 0.457219699 | None | None | N |
| S/V | 0.1862 | likely_benign | 0.1934 | benign | -0.121 | Destabilizing | 0.103 | N | 0.533 | neutral | None | None | None | None | N |
| S/W | 0.5503 | ambiguous | 0.5034 | ambiguous | -0.772 | Destabilizing | 0.992 | D | 0.7 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3351 | likely_benign | 0.3152 | benign | -0.473 | Destabilizing | 0.92 | D | 0.634 | 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.