Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20292 | 61099;61100;61101 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| N2AB | 18651 | 56176;56177;56178 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| N2A | 17724 | 53395;53396;53397 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| N2B | 11227 | 33904;33905;33906 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| Novex-1 | 11352 | 34279;34280;34281 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| Novex-2 | 11419 | 34480;34481;34482 | chr2:178590851;178590850;178590849 | chr2:179455578;179455577;179455576 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs397517647  |
-1.865 | 1.0 | D | 0.849 | 0.732 | 0.846365063961 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| W/C | rs397517647 |
-1.865 | 1.0 | D | 0.849 | 0.732 | 0.846365063961 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| W/C | rs397517647 |
-1.865 | 1.0 | D | 0.849 | 0.732 | 0.846365063961 | gnomAD-4.0.0 | 6.57713E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 0 | 0 |
| W/R | rs748357485 |
-2.234 | 1.0 | D | 0.916 | 0.878 | 0.928046224802 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 8.92E-06 | 0 |
| W/R | rs748357485 |
-2.234 | 1.0 | D | 0.916 | 0.878 | 0.928046224802 | gnomAD-4.0.0 | 6.85888E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01786E-07 | 0 | 0 |
| W/S | rs781605494 |
-3.364 | 1.0 | D | 0.896 | 0.722 | 0.94278514832 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| W/S | rs781605494 |
-3.364 | 1.0 | D | 0.896 | 0.722 | 0.94278514832 | gnomAD-4.0.0 | 3.20161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88291E-06 | 0 | 3.04044E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9937 | likely_pathogenic | 0.9944 | pathogenic | -3.341 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| W/C | 0.9946 | likely_pathogenic | 0.995 | pathogenic | -2.086 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.677864944 | None | None | N |
| W/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.658 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| W/E | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -3.547 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| W/F | 0.6371 | likely_pathogenic | 0.5959 | pathogenic | -2.079 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| W/G | 0.9766 | likely_pathogenic | 0.9822 | pathogenic | -3.582 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.677864944 | None | None | N |
| W/H | 0.9951 | likely_pathogenic | 0.9952 | pathogenic | -2.432 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| W/I | 0.9901 | likely_pathogenic | 0.9904 | pathogenic | -2.41 | Highly Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| W/K | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -2.799 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| W/L | 0.9683 | likely_pathogenic | 0.9669 | pathogenic | -2.41 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.676855923 | None | None | N |
| W/M | 0.9924 | likely_pathogenic | 0.9916 | pathogenic | -1.898 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| W/N | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -3.521 | Highly Destabilizing | 1.0 | D | 0.926 | deleterious | None | None | None | None | N |
| W/P | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -2.751 | Highly Destabilizing | 1.0 | D | 0.929 | deleterious | None | None | None | None | N |
| W/Q | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.368 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| W/R | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -2.442 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | D | 0.677864944 | None | None | N |
| W/S | 0.9906 | likely_pathogenic | 0.992 | pathogenic | -3.675 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | D | 0.661845583 | None | None | N |
| W/T | 0.996 | likely_pathogenic | 0.9965 | pathogenic | -3.493 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| W/V | 0.9866 | likely_pathogenic | 0.9864 | pathogenic | -2.751 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| W/Y | 0.9302 | likely_pathogenic | 0.9158 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.854 | 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.