Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27994 | 84205;84206;84207 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| N2AB | 26353 | 79282;79283;79284 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| N2A | 25426 | 76501;76502;76503 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| N2B | 18929 | 57010;57011;57012 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| Novex-1 | 19054 | 57385;57386;57387 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| Novex-2 | 19121 | 57586;57587;57588 | chr2:178562152;178562151;178562150 | chr2:179426879;179426878;179426877 |
| 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/L | None | None | 0.068 | D | 0.61 | 0.309 | 0.372268306217 | gnomAD-4.0.0 | 3.18557E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72001E-06 | 0 | 0 |
| V/M | rs572706568  |
-0.467 | 0.782 | D | 0.699 | 0.439 | 0.485634191555 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93125E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs572706568 |
-0.467 | 0.782 | D | 0.699 | 0.439 | 0.485634191555 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| V/M | rs572706568 |
-0.467 | 0.782 | D | 0.699 | 0.439 | 0.485634191555 | gnomAD-4.0.0 | 6.56711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93573E-04 | None | 0 | 0 | 0 | 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 | 0.1918 | likely_benign | 0.213 | benign | -1.557 | Destabilizing | 0.505 | D | 0.661 | neutral | D | 0.540421726 | None | None | N |
| V/C | 0.688 | likely_pathogenic | 0.6991 | pathogenic | -1.138 | Destabilizing | 0.991 | D | 0.756 | deleterious | None | None | None | None | N |
| V/D | 0.8419 | likely_pathogenic | 0.8915 | pathogenic | -1.113 | Destabilizing | 0.906 | D | 0.849 | deleterious | None | None | None | None | N |
| V/E | 0.7378 | likely_pathogenic | 0.8005 | pathogenic | -1.048 | Destabilizing | 0.879 | D | 0.84 | deleterious | D | 0.604347368 | None | None | N |
| V/F | 0.2758 | likely_benign | 0.3199 | benign | -1.092 | Destabilizing | 0.704 | D | 0.788 | deleterious | None | None | None | None | N |
| V/G | 0.3713 | ambiguous | 0.4326 | ambiguous | -1.948 | Destabilizing | 0.879 | D | 0.809 | deleterious | D | 0.578809256 | None | None | N |
| V/H | 0.8596 | likely_pathogenic | 0.8872 | pathogenic | -1.465 | Destabilizing | 0.991 | D | 0.849 | deleterious | None | None | None | None | N |
| V/I | 0.0796 | likely_benign | 0.0788 | benign | -0.559 | Destabilizing | 0.004 | N | 0.251 | neutral | None | None | None | None | N |
| V/K | 0.7314 | likely_pathogenic | 0.7818 | pathogenic | -1.188 | Destabilizing | 0.906 | D | 0.844 | deleterious | None | None | None | None | N |
| V/L | 0.2392 | likely_benign | 0.2662 | benign | -0.559 | Destabilizing | 0.068 | N | 0.61 | neutral | D | 0.548093878 | None | None | N |
| V/M | 0.1876 | likely_benign | 0.212 | benign | -0.527 | Destabilizing | 0.782 | D | 0.699 | prob.neutral | D | 0.603943759 | None | None | N |
| V/N | 0.6522 | likely_pathogenic | 0.7272 | pathogenic | -1.078 | Destabilizing | 0.967 | D | 0.854 | deleterious | None | None | None | None | N |
| V/P | 0.6598 | likely_pathogenic | 0.8233 | pathogenic | -0.857 | Destabilizing | 0.967 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Q | 0.6873 | likely_pathogenic | 0.7372 | pathogenic | -1.123 | Destabilizing | 0.967 | D | 0.847 | deleterious | None | None | None | None | N |
| V/R | 0.6703 | likely_pathogenic | 0.7313 | pathogenic | -0.83 | Destabilizing | 0.906 | D | 0.854 | deleterious | None | None | None | None | N |
| V/S | 0.3692 | ambiguous | 0.4229 | ambiguous | -1.708 | Destabilizing | 0.906 | D | 0.829 | deleterious | None | None | None | None | N |
| V/T | 0.2717 | likely_benign | 0.2985 | benign | -1.504 | Destabilizing | 0.575 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/W | 0.8958 | likely_pathogenic | 0.9141 | pathogenic | -1.311 | Destabilizing | 0.022 | N | 0.705 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7256 | likely_pathogenic | 0.7593 | pathogenic | -0.988 | Destabilizing | 0.704 | D | 0.783 | deleterious | 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.