Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30754 | 92485;92486;92487 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| N2AB | 29113 | 87562;87563;87564 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| N2A | 28186 | 84781;84782;84783 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| N2B | 21689 | 65290;65291;65292 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| Novex-1 | 21814 | 65665;65666;65667 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| Novex-2 | 21881 | 65866;65867;65868 | chr2:178549366;178549365;178549364 | chr2:179414093;179414092;179414091 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | D | 0.858 | 0.819 | 0.896455313471 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| Y/D | rs369857502  |
None | 1.0 | D | 0.888 | 0.814 | None | gnomAD-4.0.0 | 2.05259E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69838E-06 | 0 | 0 |
| Y/H | rs369857502 |
-2.905 | 1.0 | D | 0.836 | 0.8 | 0.786328330707 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/H | rs369857502 |
-2.905 | 1.0 | D | 0.836 | 0.8 | 0.786328330707 | gnomAD-4.0.0 | 6.84198E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9976 | likely_pathogenic | 0.9983 | pathogenic | -3.592 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/C | 0.9706 | likely_pathogenic | 0.9769 | pathogenic | -2.162 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | D | 0.682765428 | None | None | N |
| Y/D | 0.9948 | likely_pathogenic | 0.996 | pathogenic | -3.951 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | D | 0.682967232 | None | None | N |
| Y/E | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -3.734 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| Y/F | 0.431 | ambiguous | 0.3807 | ambiguous | -1.428 | Destabilizing | 0.999 | D | 0.653 | neutral | D | 0.577878803 | None | None | N |
| Y/G | 0.9888 | likely_pathogenic | 0.9925 | pathogenic | -4.011 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| Y/H | 0.9869 | likely_pathogenic | 0.987 | pathogenic | -2.583 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.666342459 | None | None | N |
| Y/I | 0.9834 | likely_pathogenic | 0.9843 | pathogenic | -2.169 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| Y/K | 0.9988 | likely_pathogenic | 0.999 | pathogenic | -2.642 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| Y/L | 0.9536 | likely_pathogenic | 0.959 | pathogenic | -2.169 | Highly Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| Y/M | 0.9869 | likely_pathogenic | 0.9893 | pathogenic | -1.892 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| Y/N | 0.9729 | likely_pathogenic | 0.9794 | pathogenic | -3.47 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.682765428 | None | None | N |
| Y/P | 0.9991 | likely_pathogenic | 0.9994 | pathogenic | -2.664 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| Y/Q | 0.9987 | likely_pathogenic | 0.999 | pathogenic | -3.204 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| Y/R | 0.9963 | likely_pathogenic | 0.9969 | pathogenic | -2.367 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| Y/S | 0.9931 | likely_pathogenic | 0.9949 | pathogenic | -3.803 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.682765428 | None | None | N |
| Y/T | 0.9968 | likely_pathogenic | 0.9977 | pathogenic | -3.465 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| Y/V | 0.971 | likely_pathogenic | 0.9739 | pathogenic | -2.664 | Highly Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| Y/W | 0.9233 | likely_pathogenic | 0.9165 | pathogenic | -0.653 | Destabilizing | 1.0 | D | 0.831 | 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.