Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27407 | 82444;82445;82446 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| N2AB | 25766 | 77521;77522;77523 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| N2A | 24839 | 74740;74741;74742 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| N2B | 18342 | 55249;55250;55251 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| Novex-1 | 18467 | 55624;55625;55626 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| Novex-2 | 18534 | 55825;55826;55827 | chr2:178563913;178563912;178563911 | chr2:179428640;179428639;179428638 |
| 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/T | rs376037252  |
-3.483 | 0.997 | N | 0.712 | 0.476 | None | gnomAD-2.1.1 | 5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.01655E-04 | 0 |
| I/T | rs376037252 |
-3.483 | 0.997 | N | 0.712 | 0.476 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17623E-04 | 0 | 4.78011E-04 |
| I/T | rs376037252 |
-3.483 | 0.997 | N | 0.712 | 0.476 | 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/T | rs376037252 |
-3.483 | 0.997 | N | 0.712 | 0.476 | None | gnomAD-4.0.0 | 7.5603E-05 | None | None | None | None | N | None | 1.33305E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.83281E-05 | 1.09808E-05 | 6.40205E-05 |
| I/V | rs752734736 |
-2.058 | 0.798 | N | 0.267 | 0.141 | 0.411401001288 | gnomAD-4.0.0 | 1.59139E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7968 | likely_pathogenic | 0.7616 | pathogenic | -3.043 | Highly Destabilizing | 0.983 | D | 0.663 | neutral | None | None | None | None | N |
| I/C | 0.955 | likely_pathogenic | 0.9545 | pathogenic | -2.111 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -3.638 | Highly Destabilizing | 0.999 | D | 0.901 | deleterious | None | None | None | None | N |
| I/E | 0.9971 | likely_pathogenic | 0.9961 | pathogenic | -3.305 | Highly Destabilizing | 0.999 | D | 0.895 | deleterious | None | None | None | None | N |
| I/F | 0.8088 | likely_pathogenic | 0.801 | pathogenic | -1.815 | Destabilizing | 0.994 | D | 0.632 | neutral | D | 0.533000428 | None | None | N |
| I/G | 0.99 | likely_pathogenic | 0.9872 | pathogenic | -3.648 | Highly Destabilizing | 0.999 | D | 0.895 | deleterious | None | None | None | None | N |
| I/H | 0.9975 | likely_pathogenic | 0.9969 | pathogenic | -3.284 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| I/K | 0.9947 | likely_pathogenic | 0.9932 | pathogenic | -2.333 | Highly Destabilizing | 0.998 | D | 0.894 | deleterious | None | None | None | None | N |
| I/L | 0.1718 | likely_benign | 0.1664 | benign | -1.193 | Destabilizing | 0.054 | N | 0.271 | neutral | N | 0.477715189 | None | None | N |
| I/M | 0.3081 | likely_benign | 0.2932 | benign | -1.41 | Destabilizing | 0.994 | D | 0.637 | neutral | N | 0.493246746 | None | None | N |
| I/N | 0.994 | likely_pathogenic | 0.9912 | pathogenic | -3.111 | Highly Destabilizing | 0.999 | D | 0.915 | deleterious | D | 0.533253917 | None | None | N |
| I/P | 0.9919 | likely_pathogenic | 0.9907 | pathogenic | -1.806 | Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| I/Q | 0.9954 | likely_pathogenic | 0.9939 | pathogenic | -2.717 | Highly Destabilizing | 0.999 | D | 0.913 | deleterious | None | None | None | None | N |
| I/R | 0.9907 | likely_pathogenic | 0.9881 | pathogenic | -2.431 | Highly Destabilizing | 0.999 | D | 0.912 | deleterious | None | None | None | None | N |
| I/S | 0.9667 | likely_pathogenic | 0.9532 | pathogenic | -3.61 | Highly Destabilizing | 0.999 | D | 0.822 | deleterious | D | 0.533253917 | None | None | N |
| I/T | 0.7154 | likely_pathogenic | 0.6646 | pathogenic | -3.112 | Highly Destabilizing | 0.997 | D | 0.712 | prob.delet. | N | 0.521479538 | None | None | N |
| I/V | 0.0865 | likely_benign | 0.0856 | benign | -1.806 | Destabilizing | 0.798 | D | 0.267 | neutral | N | 0.390221129 | None | None | N |
| I/W | 0.9952 | likely_pathogenic | 0.9952 | pathogenic | -2.123 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| I/Y | 0.9903 | likely_pathogenic | 0.9892 | pathogenic | -2.035 | Highly Destabilizing | 0.999 | D | 0.753 | 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.