Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24152 | 72679;72680;72681 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| N2AB | 22511 | 67756;67757;67758 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| N2A | 21584 | 64975;64976;64977 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| N2B | 15087 | 45484;45485;45486 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| Novex-1 | 15212 | 45859;45860;45861 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| Novex-2 | 15279 | 46060;46061;46062 | chr2:178573678;178573677;178573676 | chr2:179438405;179438404;179438403 |
| 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/A | None | None | 1.0 | N | 0.611 | 0.452 | 0.3691244813 | gnomAD-4.0.0 | 7.32921E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.37842E-07 | 0 | 0 |
| G/D | rs752412425  |
-0.179 | 1.0 | N | 0.682 | 0.519 | 0.437314048365 | gnomAD-2.1.1 | 5.65E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.16E-05 | 0 |
| G/D | rs752412425 |
-0.179 | 1.0 | N | 0.682 | 0.519 | 0.437314048365 | gnomAD-4.0.0 | 5.86337E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.50273E-06 | 0 | 0 |
| G/R | rs538368683 |
-0.165 | 1.0 | N | 0.791 | 0.538 | 0.637055726968 | gnomAD-2.1.1 | 1.69E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.0562E-04 | None | 0 | 0 | 0 |
| G/R | rs538368683 |
-0.165 | 1.0 | N | 0.791 | 0.538 | 0.637055726968 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| G/R | rs538368683 |
-0.165 | 1.0 | N | 0.791 | 0.538 | 0.637055726968 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| G/R | rs538368683 |
-0.165 | 1.0 | N | 0.791 | 0.538 | 0.637055726968 | gnomAD-4.0.0 | 1.02443E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.23605E-04 | 0 |
| G/V | rs752412425 |
None | 1.0 | D | 0.788 | 0.48 | 0.676136979346 | gnomAD-4.0.0 | 7.32921E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.37842E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.6942 | likely_pathogenic | 0.6694 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.503683863 | None | None | I |
| G/C | 0.6772 | likely_pathogenic | 0.697 | pathogenic | -0.814 | Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.529994553 | None | None | I |
| G/D | 0.9286 | likely_pathogenic | 0.9206 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.515155527 | None | None | I |
| G/E | 0.9363 | likely_pathogenic | 0.9285 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| G/F | 0.9607 | likely_pathogenic | 0.9578 | pathogenic | -0.972 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| G/H | 0.9527 | likely_pathogenic | 0.9484 | pathogenic | -0.298 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| G/I | 0.9544 | likely_pathogenic | 0.9532 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| G/K | 0.9654 | likely_pathogenic | 0.9645 | pathogenic | -0.514 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| G/L | 0.944 | likely_pathogenic | 0.9402 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| G/M | 0.9486 | likely_pathogenic | 0.9444 | pathogenic | -0.487 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| G/N | 0.8851 | likely_pathogenic | 0.8627 | pathogenic | -0.191 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| G/P | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -0.296 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| G/Q | 0.925 | likely_pathogenic | 0.9163 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| G/R | 0.918 | likely_pathogenic | 0.914 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.509483988 | None | None | I |
| G/S | 0.5317 | ambiguous | 0.5137 | ambiguous | -0.328 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.502416415 | None | None | I |
| G/T | 0.8821 | likely_pathogenic | 0.8773 | pathogenic | -0.427 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| G/V | 0.9191 | likely_pathogenic | 0.9156 | pathogenic | -0.296 | Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.558605739 | None | None | I |
| G/W | 0.9545 | likely_pathogenic | 0.952 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| G/Y | 0.9454 | likely_pathogenic | 0.9421 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.769 | 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.