Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24707 | 74344;74345;74346 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| N2AB | 23066 | 69421;69422;69423 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| N2A | 22139 | 66640;66641;66642 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| N2B | 15642 | 47149;47150;47151 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| Novex-1 | 15767 | 47524;47525;47526 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| Novex-2 | 15834 | 47725;47726;47727 | chr2:178572013;178572012;178572011 | chr2:179436740;179436739;179436738 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.999 | D | 0.66 | 0.379 | 0.622959606287 | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53049E-05 | None | 1.87406E-05 | 0 | 0 | 0 | 0 |
| V/E | rs780299418  |
None | 0.999 | D | 0.89 | 0.542 | 0.783232054654 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/E | rs780299418 |
None | 0.999 | D | 0.89 | 0.542 | 0.783232054654 | gnomAD-4.0.0 | 1.23978E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69552E-06 | 0 | 0 |
| V/M | rs2154169785 |
None | 1.0 | D | 0.657 | 0.333 | 0.572001775666 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85971E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7235 | likely_pathogenic | 0.7539 | pathogenic | -1.683 | Destabilizing | 0.999 | D | 0.66 | prob.neutral | D | 0.522537543 | None | None | N |
| V/C | 0.9411 | likely_pathogenic | 0.9479 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| V/D | 0.9942 | likely_pathogenic | 0.9942 | pathogenic | -2.093 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| V/E | 0.9758 | likely_pathogenic | 0.9745 | pathogenic | -1.858 | Destabilizing | 0.999 | D | 0.89 | deleterious | D | 0.522791033 | None | None | N |
| V/F | 0.6623 | likely_pathogenic | 0.6633 | pathogenic | -0.974 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/G | 0.8963 | likely_pathogenic | 0.9125 | pathogenic | -2.201 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | D | 0.523551501 | None | None | N |
| V/H | 0.9893 | likely_pathogenic | 0.9888 | pathogenic | -1.81 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/I | 0.0961 | likely_benign | 0.1003 | benign | -0.24 | Destabilizing | 0.988 | D | 0.61 | neutral | None | None | None | None | N |
| V/K | 0.9791 | likely_pathogenic | 0.9785 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| V/L | 0.5579 | ambiguous | 0.5985 | pathogenic | -0.24 | Destabilizing | 0.984 | D | 0.643 | neutral | N | 0.47395877 | None | None | N |
| V/M | 0.4648 | ambiguous | 0.4867 | ambiguous | -0.289 | Destabilizing | 1.0 | D | 0.657 | prob.neutral | D | 0.523044522 | None | None | N |
| V/N | 0.9761 | likely_pathogenic | 0.9759 | pathogenic | -1.785 | Destabilizing | 0.998 | D | 0.878 | deleterious | None | None | None | None | N |
| V/P | 0.9917 | likely_pathogenic | 0.9926 | pathogenic | -0.695 | Destabilizing | 0.998 | D | 0.887 | deleterious | None | None | None | None | N |
| V/Q | 0.9625 | likely_pathogenic | 0.9593 | pathogenic | -1.584 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| V/R | 0.9688 | likely_pathogenic | 0.9678 | pathogenic | -1.326 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| V/S | 0.9164 | likely_pathogenic | 0.9258 | pathogenic | -2.386 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| V/T | 0.7729 | likely_pathogenic | 0.782 | pathogenic | -1.994 | Destabilizing | 0.998 | D | 0.521 | neutral | None | None | None | None | N |
| V/W | 0.9938 | likely_pathogenic | 0.9942 | pathogenic | -1.415 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| V/Y | 0.9636 | likely_pathogenic | 0.9648 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.819 | 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.