Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25208 | 75847;75848;75849 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| N2AB | 23567 | 70924;70925;70926 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| N2A | 22640 | 68143;68144;68145 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| N2B | 16143 | 48652;48653;48654 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| Novex-1 | 16268 | 49027;49028;49029 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| Novex-2 | 16335 | 49228;49229;49230 | chr2:178570510;178570509;178570508 | chr2:179435237;179435236;179435235 |
| 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/H | rs549335677  |
-2.611 | 0.999 | D | 0.921 | 0.788 | 0.754827158073 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/H | rs549335677 |
-2.611 | 0.999 | D | 0.921 | 0.788 | 0.754827158073 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/H | rs549335677 |
-2.611 | 0.999 | D | 0.921 | 0.788 | 0.754827158073 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/H | rs549335677 |
-2.611 | 0.999 | D | 0.921 | 0.788 | 0.754827158073 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | N | None | 2.40755E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | None | None | 0.989 | D | 0.907 | 0.808 | 0.750271218199 | gnomAD-4.0.0 | 1.59238E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85956E-06 | 0 | 0 |
| P/T | rs1484393725 |
None | 0.978 | D | 0.819 | 0.77 | 0.759945495233 | gnomAD-4.0.0 | 1.59235E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3694 | ambiguous | 0.3783 | ambiguous | -2.102 | Highly Destabilizing | 0.928 | D | 0.797 | deleterious | D | 0.619961325 | None | None | N |
| P/C | 0.7216 | likely_pathogenic | 0.7485 | pathogenic | -1.714 | Destabilizing | 0.999 | D | 0.923 | deleterious | None | None | None | None | N |
| P/D | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -3.254 | Highly Destabilizing | 0.997 | D | 0.839 | deleterious | None | None | None | None | N |
| P/E | 0.9933 | likely_pathogenic | 0.9948 | pathogenic | -3.024 | Highly Destabilizing | 0.992 | D | 0.837 | deleterious | None | None | None | None | N |
| P/F | 0.9964 | likely_pathogenic | 0.9967 | pathogenic | -1.155 | Destabilizing | 0.991 | D | 0.94 | deleterious | None | None | None | None | N |
| P/G | 0.9575 | likely_pathogenic | 0.963 | pathogenic | -2.627 | Highly Destabilizing | 0.992 | D | 0.886 | deleterious | None | None | None | None | N |
| P/H | 0.9928 | likely_pathogenic | 0.9941 | pathogenic | -2.524 | Highly Destabilizing | 0.999 | D | 0.921 | deleterious | D | 0.652837625 | None | None | N |
| P/I | 0.7726 | likely_pathogenic | 0.7487 | pathogenic | -0.618 | Destabilizing | 0.968 | D | 0.909 | deleterious | None | None | None | None | N |
| P/K | 0.9967 | likely_pathogenic | 0.9976 | pathogenic | -1.866 | Destabilizing | 0.992 | D | 0.841 | deleterious | None | None | None | None | N |
| P/L | 0.738 | likely_pathogenic | 0.7463 | pathogenic | -0.618 | Destabilizing | 0.085 | N | 0.797 | deleterious | D | 0.652434016 | None | None | N |
| P/M | 0.9194 | likely_pathogenic | 0.9235 | pathogenic | -0.762 | Destabilizing | 0.996 | D | 0.933 | deleterious | None | None | None | None | N |
| P/N | 0.9939 | likely_pathogenic | 0.9948 | pathogenic | -2.272 | Highly Destabilizing | 0.997 | D | 0.915 | deleterious | None | None | None | None | N |
| P/Q | 0.9847 | likely_pathogenic | 0.9876 | pathogenic | -2.087 | Highly Destabilizing | 0.997 | D | 0.859 | deleterious | None | None | None | None | N |
| P/R | 0.9902 | likely_pathogenic | 0.9922 | pathogenic | -1.705 | Destabilizing | 0.989 | D | 0.907 | deleterious | D | 0.652635821 | None | None | N |
| P/S | 0.8217 | likely_pathogenic | 0.8302 | pathogenic | -2.766 | Highly Destabilizing | 0.989 | D | 0.826 | deleterious | D | 0.636414655 | None | None | N |
| P/T | 0.6925 | likely_pathogenic | 0.6927 | pathogenic | -2.41 | Highly Destabilizing | 0.978 | D | 0.819 | deleterious | D | 0.63661646 | None | None | N |
| P/V | 0.4705 | ambiguous | 0.441 | ambiguous | -1.089 | Destabilizing | 0.968 | D | 0.854 | deleterious | None | None | None | None | N |
| P/W | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -1.822 | Destabilizing | 0.999 | D | 0.912 | deleterious | None | None | None | None | N |
| P/Y | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -1.44 | Destabilizing | 0.998 | D | 0.943 | 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.