Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28372 | 85339;85340;85341 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| N2AB | 26731 | 80416;80417;80418 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| N2A | 25804 | 77635;77636;77637 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| N2B | 19307 | 58144;58145;58146 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| Novex-1 | 19432 | 58519;58520;58521 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| Novex-2 | 19499 | 58720;58721;58722 | chr2:178561018;178561017;178561016 | chr2:179425745;179425744;179425743 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/E | rs190721759  |
-0.759 | 1.0 | D | 0.859 | 0.818 | None | gnomAD-2.1.1 | 1.28618E-04 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.42665E-04 | 2.80978E-04 |
| G/E | rs190721759 |
-0.759 | 1.0 | D | 0.859 | 0.818 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.3231E-04 | 0 | 0 |
| G/E | rs190721759 |
-0.759 | 1.0 | D | 0.859 | 0.818 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| G/E | rs190721759 |
-0.759 | 1.0 | D | 0.859 | 0.818 | None | gnomAD-4.0.0 | 3.24063E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.2549E-04 | 1.09789E-05 | 3.20092E-04 |
| G/R | rs1323161898 |
-0.282 | 1.0 | D | 0.873 | 0.852 | 0.900311829425 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| G/R | rs1323161898 |
-0.282 | 1.0 | D | 0.873 | 0.852 | 0.900311829425 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5707 | likely_pathogenic | 0.4873 | ambiguous | -0.477 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.587608281 | None | None | I |
| G/C | 0.6222 | likely_pathogenic | 0.5655 | pathogenic | -0.909 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| G/D | 0.522 | ambiguous | 0.4769 | ambiguous | -1.133 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | I |
| G/E | 0.6202 | likely_pathogenic | 0.5381 | ambiguous | -1.307 | Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.606393976 | None | None | I |
| G/F | 0.9524 | likely_pathogenic | 0.9343 | pathogenic | -1.248 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| G/H | 0.7357 | likely_pathogenic | 0.6746 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| G/I | 0.9606 | likely_pathogenic | 0.94 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| G/K | 0.6245 | likely_pathogenic | 0.5702 | pathogenic | -1.049 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| G/L | 0.8989 | likely_pathogenic | 0.8663 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| G/M | 0.9094 | likely_pathogenic | 0.8748 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| G/N | 0.587 | likely_pathogenic | 0.5287 | ambiguous | -0.67 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| G/P | 0.9925 | likely_pathogenic | 0.9877 | pathogenic | -0.536 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| G/Q | 0.6283 | likely_pathogenic | 0.5558 | ambiguous | -1.038 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| G/R | 0.5019 | ambiguous | 0.4318 | ambiguous | -0.474 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.60800841 | None | None | I |
| G/S | 0.3062 | likely_benign | 0.2572 | benign | -0.753 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| G/T | 0.688 | likely_pathogenic | 0.6099 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| G/V | 0.9034 | likely_pathogenic | 0.8633 | pathogenic | -0.536 | Destabilizing | 1.0 | D | 0.842 | deleterious | D | 0.645588724 | None | None | I |
| G/W | 0.8088 | likely_pathogenic | 0.7547 | pathogenic | -1.372 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| G/Y | 0.8863 | likely_pathogenic | 0.8466 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.849 | deleterious | 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.