Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14158 | 42697;42698;42699 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| N2AB | 12517 | 37774;37775;37776 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| N2A | 11590 | 34993;34994;34995 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| N2B | 5093 | 15502;15503;15504 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| Novex-1 | 5218 | 15877;15878;15879 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| Novex-2 | 5285 | 16078;16079;16080 | chr2:178634027;178634026;178634025 | chr2:179498754;179498753;179498752 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs2060122664  |
None | 0.981 | N | 0.468 | 0.245 | 0.21737058555 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs2060122664 |
None | 0.981 | N | 0.468 | 0.245 | 0.21737058555 | gnomAD-4.0.0 | 6.57635E-06 | None | None | None | None | N | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs373227762 |
0.038 | 0.999 | D | 0.8 | 0.439 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| T/I | rs373227762 |
0.038 | 0.999 | D | 0.8 | 0.439 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/I | rs373227762 |
0.038 | 0.999 | D | 0.8 | 0.439 | None | gnomAD-4.0.0 | 6.26137E-05 | None | None | None | None | N | None | 2.67258E-05 | 1.66811E-05 | None | 0 | 0 | None | 0 | 0 | 8.13921E-05 | 0 | 3.20379E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0985 | likely_benign | 0.1077 | benign | -0.703 | Destabilizing | 0.981 | D | 0.468 | neutral | N | 0.441336854 | None | None | N |
| T/C | 0.5772 | likely_pathogenic | 0.6202 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| T/D | 0.4525 | ambiguous | 0.5115 | ambiguous | -0.259 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| T/E | 0.3587 | ambiguous | 0.4054 | ambiguous | -0.284 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/F | 0.353 | ambiguous | 0.4142 | ambiguous | -0.829 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| T/G | 0.3401 | ambiguous | 0.3929 | ambiguous | -0.937 | Destabilizing | 0.997 | D | 0.628 | neutral | None | None | None | None | N |
| T/H | 0.3455 | ambiguous | 0.3847 | ambiguous | -1.203 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| T/I | 0.2415 | likely_benign | 0.2894 | benign | -0.178 | Destabilizing | 0.999 | D | 0.8 | deleterious | D | 0.58709662 | None | None | N |
| T/K | 0.1899 | likely_benign | 0.2368 | benign | -0.756 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.442426361 | None | None | N |
| T/L | 0.147 | likely_benign | 0.1711 | benign | -0.178 | Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | N |
| T/M | 0.0961 | likely_benign | 0.1007 | benign | 0.159 | Stabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| T/N | 0.1442 | likely_benign | 0.1697 | benign | -0.602 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| T/P | 0.155 | likely_benign | 0.1785 | benign | -0.321 | Destabilizing | 0.999 | D | 0.803 | deleterious | N | 0.465833731 | None | None | N |
| T/Q | 0.2855 | likely_benign | 0.3223 | benign | -0.821 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| T/R | 0.1705 | likely_benign | 0.2019 | benign | -0.446 | Destabilizing | 0.999 | D | 0.803 | deleterious | N | 0.453938051 | None | None | N |
| T/S | 0.1478 | likely_benign | 0.164 | benign | -0.863 | Destabilizing | 0.905 | D | 0.334 | neutral | N | 0.444671376 | None | None | N |
| T/V | 0.1933 | likely_benign | 0.2333 | benign | -0.321 | Destabilizing | 0.998 | D | 0.541 | neutral | None | None | None | None | N |
| T/W | 0.6797 | likely_pathogenic | 0.7342 | pathogenic | -0.761 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| T/Y | 0.3782 | ambiguous | 0.4393 | ambiguous | -0.541 | Destabilizing | 1.0 | D | 0.835 | 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.