Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17731 | 53416;53417;53418 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| N2AB | 16090 | 48493;48494;48495 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| N2A | 15163 | 45712;45713;45714 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| N2B | 8666 | 26221;26222;26223 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| Novex-1 | 8791 | 26596;26597;26598 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| Novex-2 | 8858 | 26797;26798;26799 | chr2:178607497;178607496;178607495 | chr2:179472224;179472223;179472222 |
| 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/N | rs72646809  |
-2.899 | 1.0 | D | 0.901 | 0.846 | 0.93495532163 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs72646809 |
-2.899 | 1.0 | D | 0.901 | 0.846 | 0.93495532163 | gnomAD-4.0.0 | 1.36878E-06 | None | None | None | None | N | None | 5.98193E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs72646809 |
-3.166 | 1.0 | D | 0.834 | 0.801 | None | gnomAD-2.1.1 | 1.37245E-02 | None | None | None | None | N | None | 2.19117E-03 | 6.84389E-03 | None | 3.00483E-02 | 5.13E-05 | None | 9.41238E-03 | None | 4.10105E-02 | 1.4082E-02 | 1.69896E-02 |
| I/T | rs72646809 |
-3.166 | 1.0 | D | 0.834 | 0.801 | None | gnomAD-3.1.2 | 1.10997E-02 | None | None | None | None | N | None | 2.51014E-03 | 4.72007E-03 | 3.28947E-03 | 3.60438E-02 | 0 | None | 4.71165E-02 | 2.21519E-02 | 1.1924E-02 | 8.27472E-03 | 1.24283E-02 |
| I/T | rs72646809 |
-3.166 | 1.0 | D | 0.834 | 0.801 | None | 1000 genomes | 4.59265E-03 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 0 | 1.79E-02 | None | None | None | 3.1E-03 | None |
| I/T | rs72646809 |
-3.166 | 1.0 | D | 0.834 | 0.801 | None | gnomAD-4.0.0 | 1.1447E-02 | None | None | None | None | N | None | 2.21369E-03 | 6.61777E-03 | None | 3.08634E-02 | 2.23204E-05 | None | 3.96176E-02 | 1.33796E-02 | 1.0875E-02 | 9.00386E-03 | 1.15944E-02 |
| I/V | None | None | 0.993 | D | 0.397 | 0.455 | 0.77874929467 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86062E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9603 | likely_pathogenic | 0.9843 | pathogenic | -2.656 | Highly Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/C | 0.9387 | likely_pathogenic | 0.9714 | pathogenic | -2.055 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| I/D | 0.997 | likely_pathogenic | 0.9985 | pathogenic | -3.147 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| I/E | 0.9899 | likely_pathogenic | 0.9943 | pathogenic | -2.968 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| I/F | 0.6153 | likely_pathogenic | 0.7458 | pathogenic | -1.648 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.566684897 | None | None | N |
| I/G | 0.9924 | likely_pathogenic | 0.9973 | pathogenic | -3.166 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| I/H | 0.9821 | likely_pathogenic | 0.9913 | pathogenic | -2.633 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| I/K | 0.975 | likely_pathogenic | 0.9869 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| I/L | 0.3287 | likely_benign | 0.4077 | ambiguous | -1.198 | Destabilizing | 0.993 | D | 0.441 | neutral | D | 0.543990281 | None | None | N |
| I/M | 0.3571 | ambiguous | 0.4812 | ambiguous | -1.107 | Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.593444553 | None | None | N |
| I/N | 0.9607 | likely_pathogenic | 0.9814 | pathogenic | -2.509 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.615984166 | None | None | N |
| I/P | 0.996 | likely_pathogenic | 0.9982 | pathogenic | -1.664 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| I/Q | 0.9749 | likely_pathogenic | 0.987 | pathogenic | -2.445 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| I/R | 0.9626 | likely_pathogenic | 0.9812 | pathogenic | -1.819 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| I/S | 0.955 | likely_pathogenic | 0.9815 | pathogenic | -3.151 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.632235692 | None | None | N |
| I/T | 0.9513 | likely_pathogenic | 0.9627 | pathogenic | -2.838 | Highly Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.615580558 | None | None | N |
| I/V | 0.1641 | likely_benign | 0.1833 | benign | -1.664 | Destabilizing | 0.993 | D | 0.397 | neutral | D | 0.535490573 | None | None | N |
| I/W | 0.977 | likely_pathogenic | 0.9868 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| I/Y | 0.9481 | likely_pathogenic | 0.97 | pathogenic | -1.805 | Destabilizing | 1.0 | D | 0.837 | 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.