Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24342 | 73249;73250;73251 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| N2AB | 22701 | 68326;68327;68328 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| N2A | 21774 | 65545;65546;65547 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| N2B | 15277 | 46054;46055;46056 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| Novex-1 | 15402 | 46429;46430;46431 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| Novex-2 | 15469 | 46630;46631;46632 | chr2:178573108;178573107;178573106 | chr2:179437835;179437834;179437833 |
| 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/M | None | None | 0.951 | N | 0.657 | 0.313 | 0.37479162749 | gnomAD-4.0.0 | 2.05324E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69891E-06 | 0 | 0 |
| I/T | None | None | 0.684 | N | 0.713 | 0.398 | 0.585504228005 | gnomAD-4.0.0 | 3.18465E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.8659E-05 | 0 |
| I/V | rs1051443527  |
-0.893 | 0.012 | N | 0.206 | 0.051 | 0.214338557667 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66223E-04 |
| I/V | rs1051443527 |
-0.893 | 0.012 | N | 0.206 | 0.051 | 0.214338557667 | gnomAD-4.0.0 | 4.10641E-06 | None | None | None | None | N | None | 5.98086E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69889E-06 | 0 | 1.65722E-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 | 0.7865 | likely_pathogenic | 0.7485 | pathogenic | -2.325 | Highly Destabilizing | 0.543 | D | 0.722 | prob.delet. | None | None | None | None | N |
| I/C | 0.9168 | likely_pathogenic | 0.9138 | pathogenic | -1.653 | Destabilizing | 0.996 | D | 0.8 | deleterious | None | None | None | None | N |
| I/D | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -2.49 | Highly Destabilizing | 0.984 | D | 0.878 | deleterious | None | None | None | None | N |
| I/E | 0.9978 | likely_pathogenic | 0.9975 | pathogenic | -2.174 | Highly Destabilizing | 0.953 | D | 0.859 | deleterious | None | None | None | None | N |
| I/F | 0.5129 | ambiguous | 0.4871 | ambiguous | -1.336 | Destabilizing | 0.884 | D | 0.72 | prob.delet. | N | 0.488209036 | None | None | N |
| I/G | 0.9899 | likely_pathogenic | 0.9873 | pathogenic | -2.954 | Highly Destabilizing | 0.953 | D | 0.841 | deleterious | None | None | None | None | N |
| I/H | 0.9967 | likely_pathogenic | 0.9963 | pathogenic | -2.6 | Highly Destabilizing | 0.996 | D | 0.881 | deleterious | None | None | None | None | N |
| I/K | 0.9963 | likely_pathogenic | 0.9959 | pathogenic | -1.692 | Destabilizing | 0.953 | D | 0.843 | deleterious | None | None | None | None | N |
| I/L | 0.1063 | likely_benign | 0.1047 | benign | -0.47 | Destabilizing | 0.001 | N | 0.246 | neutral | N | 0.292968649 | None | None | N |
| I/M | 0.1949 | likely_benign | 0.1942 | benign | -0.596 | Destabilizing | 0.951 | D | 0.657 | neutral | N | 0.488555753 | None | None | N |
| I/N | 0.9938 | likely_pathogenic | 0.9925 | pathogenic | -2.293 | Highly Destabilizing | 0.979 | D | 0.88 | deleterious | N | 0.468777302 | None | None | N |
| I/P | 0.9962 | likely_pathogenic | 0.9951 | pathogenic | -1.074 | Destabilizing | 0.984 | D | 0.877 | deleterious | None | None | None | None | N |
| I/Q | 0.9959 | likely_pathogenic | 0.9952 | pathogenic | -1.933 | Destabilizing | 0.984 | D | 0.889 | deleterious | None | None | None | None | N |
| I/R | 0.9934 | likely_pathogenic | 0.9925 | pathogenic | -1.804 | Destabilizing | 0.953 | D | 0.877 | deleterious | None | None | None | None | N |
| I/S | 0.9731 | likely_pathogenic | 0.9673 | pathogenic | -3.012 | Highly Destabilizing | 0.815 | D | 0.813 | deleterious | N | 0.518531943 | None | None | N |
| I/T | 0.8345 | likely_pathogenic | 0.7922 | pathogenic | -2.515 | Highly Destabilizing | 0.684 | D | 0.713 | prob.delet. | N | 0.468270323 | None | None | N |
| I/V | 0.0702 | likely_benign | 0.0651 | benign | -1.074 | Destabilizing | 0.012 | N | 0.206 | neutral | N | 0.372933729 | None | None | N |
| I/W | 0.9925 | likely_pathogenic | 0.9917 | pathogenic | -1.709 | Destabilizing | 0.996 | D | 0.869 | deleterious | None | None | None | None | N |
| I/Y | 0.9742 | likely_pathogenic | 0.9718 | pathogenic | -1.401 | Destabilizing | 0.953 | D | 0.793 | 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.