Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32334 | 97225;97226;97227 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| N2AB | 30693 | 92302;92303;92304 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| N2A | 29766 | 89521;89522;89523 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| N2B | 23269 | 70030;70031;70032 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| Novex-1 | 23394 | 70405;70406;70407 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| Novex-2 | 23461 | 70606;70607;70608 | chr2:178542854;178542853;178542852 | chr2:179407581;179407580;179407579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs748395939  |
0.004 | 1.0 | D | 0.745 | 0.693 | 0.797824397609 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 1.79E-05 | 0 |
| P/L | rs748395939 |
0.004 | 1.0 | D | 0.745 | 0.693 | 0.797824397609 | gnomAD-4.0.0 | 2.05259E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51927E-05 | None | 0 | 0 | 1.79893E-06 | 0 | 0 |
| P/R | rs748395939 |
None | 1.0 | D | 0.767 | 0.702 | 0.661616411291 | gnomAD-4.0.0 | 4.78938E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29624E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8917 | likely_pathogenic | 0.8786 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.551087089 | None | None | I |
| P/C | 0.9865 | likely_pathogenic | 0.9848 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| P/D | 0.975 | likely_pathogenic | 0.973 | pathogenic | -0.618 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/E | 0.9664 | likely_pathogenic | 0.9634 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| P/F | 0.9873 | likely_pathogenic | 0.9868 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| P/G | 0.9672 | likely_pathogenic | 0.964 | pathogenic | -0.786 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/H | 0.9475 | likely_pathogenic | 0.9489 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| P/I | 0.9291 | likely_pathogenic | 0.922 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| P/K | 0.9649 | likely_pathogenic | 0.967 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/L | 0.8421 | likely_pathogenic | 0.8289 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.590187119 | None | None | I |
| P/M | 0.9555 | likely_pathogenic | 0.9526 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| P/N | 0.9729 | likely_pathogenic | 0.9706 | pathogenic | -0.287 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| P/Q | 0.9426 | likely_pathogenic | 0.9453 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.528209894 | None | None | I |
| P/R | 0.9402 | likely_pathogenic | 0.9442 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.605802871 | None | None | I |
| P/S | 0.9515 | likely_pathogenic | 0.9409 | pathogenic | -0.604 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.532475855 | None | None | I |
| P/T | 0.8971 | likely_pathogenic | 0.884 | pathogenic | -0.62 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | D | 0.58978351 | None | None | I |
| P/V | 0.8985 | likely_pathogenic | 0.89 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| P/W | 0.9936 | likely_pathogenic | 0.9944 | pathogenic | -0.935 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| P/Y | 0.9824 | likely_pathogenic | 0.9833 | pathogenic | -0.648 | Destabilizing | 1.0 | D | 0.791 | 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.