Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17854 | 53785;53786;53787 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| N2AB | 16213 | 48862;48863;48864 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| N2A | 15286 | 46081;46082;46083 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| N2B | 8789 | 26590;26591;26592 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| Novex-1 | 8914 | 26965;26966;26967 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| Novex-2 | 8981 | 27166;27167;27168 | chr2:178607042;178607041;178607040 | chr2:179471769;179471768;179471767 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs375796420  |
-1.673 | 0.994 | N | 0.901 | 0.475 | None | gnomAD-2.1.1 | 3.24E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.20048E-04 | 3.93E-05 | 1.41683E-04 |
| I/N | rs375796420 |
-1.673 | 0.994 | N | 0.901 | 0.475 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 5.89E-05 | 0 | 4.78011E-04 |
| I/N | rs375796420 |
-1.673 | 0.994 | N | 0.901 | 0.475 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/N | rs375796420 |
-1.673 | 0.994 | N | 0.901 | 0.475 | None | gnomAD-4.0.0 | 1.67659E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.81274E-05 | 0 | 1.7817E-05 | 0 | 1.60483E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9007 | likely_pathogenic | 0.9136 | pathogenic | -2.321 | Highly Destabilizing | 0.904 | D | 0.588 | neutral | None | None | None | None | N |
| I/C | 0.9061 | likely_pathogenic | 0.9177 | pathogenic | -1.434 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| I/D | 0.9918 | likely_pathogenic | 0.9945 | pathogenic | -2.531 | Highly Destabilizing | 0.995 | D | 0.909 | deleterious | None | None | None | None | N |
| I/E | 0.9703 | likely_pathogenic | 0.9747 | pathogenic | -2.324 | Highly Destabilizing | 0.995 | D | 0.911 | deleterious | None | None | None | None | N |
| I/F | 0.4058 | ambiguous | 0.4557 | ambiguous | -1.378 | Destabilizing | 0.961 | D | 0.641 | neutral | N | 0.473201982 | None | None | N |
| I/G | 0.9821 | likely_pathogenic | 0.9856 | pathogenic | -2.829 | Highly Destabilizing | 0.995 | D | 0.903 | deleterious | None | None | None | None | N |
| I/H | 0.9434 | likely_pathogenic | 0.9605 | pathogenic | -2.107 | Highly Destabilizing | 0.999 | D | 0.871 | deleterious | None | None | None | None | N |
| I/K | 0.9354 | likely_pathogenic | 0.9469 | pathogenic | -1.821 | Destabilizing | 0.985 | D | 0.905 | deleterious | None | None | None | None | N |
| I/L | 0.209 | likely_benign | 0.228 | benign | -0.868 | Destabilizing | 0.009 | N | 0.214 | neutral | N | 0.469653129 | None | None | N |
| I/M | 0.2672 | likely_benign | 0.28 | benign | -0.69 | Destabilizing | 0.961 | D | 0.645 | neutral | N | 0.466961012 | None | None | N |
| I/N | 0.9258 | likely_pathogenic | 0.9466 | pathogenic | -2.109 | Highly Destabilizing | 0.994 | D | 0.901 | deleterious | N | 0.485318756 | None | None | N |
| I/P | 0.992 | likely_pathogenic | 0.993 | pathogenic | -1.333 | Destabilizing | 0.995 | D | 0.903 | deleterious | None | None | None | None | N |
| I/Q | 0.9241 | likely_pathogenic | 0.9369 | pathogenic | -2.021 | Highly Destabilizing | 0.995 | D | 0.877 | deleterious | None | None | None | None | N |
| I/R | 0.9061 | likely_pathogenic | 0.9242 | pathogenic | -1.472 | Destabilizing | 0.985 | D | 0.898 | deleterious | None | None | None | None | N |
| I/S | 0.9171 | likely_pathogenic | 0.9356 | pathogenic | -2.77 | Highly Destabilizing | 0.981 | D | 0.75 | deleterious | N | 0.482276882 | None | None | N |
| I/T | 0.8153 | likely_pathogenic | 0.855 | pathogenic | -2.42 | Highly Destabilizing | 0.981 | D | 0.717 | prob.delet. | N | 0.471681045 | None | None | N |
| I/V | 0.0999 | likely_benign | 0.1019 | benign | -1.333 | Destabilizing | 0.39 | N | 0.415 | neutral | N | 0.447863923 | None | None | N |
| I/W | 0.9647 | likely_pathogenic | 0.9717 | pathogenic | -1.71 | Destabilizing | 0.999 | D | 0.816 | deleterious | None | None | None | None | N |
| I/Y | 0.8566 | likely_pathogenic | 0.8878 | pathogenic | -1.401 | Destabilizing | 0.985 | D | 0.736 | 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.