Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32473 | 97642;97643;97644 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| N2AB | 30832 | 92719;92720;92721 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| N2A | 29905 | 89938;89939;89940 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| N2B | 23408 | 70447;70448;70449 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| Novex-1 | 23533 | 70822;70823;70824 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| Novex-2 | 23600 | 71023;71024;71025 | chr2:178542339;178542338;178542337 | chr2:179407066;179407065;179407064 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs371924787  |
-1.693 | 1.0 | D | 0.874 | 0.539 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 2.68E-05 | 0 |
| R/C | rs371924787 |
-1.693 | 1.0 | D | 0.874 | 0.539 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.80307E-04 |
| R/C | rs371924787 |
-1.693 | 1.0 | D | 0.874 | 0.539 | None | gnomAD-4.0.0 | 2.2317E-05 | None | None | None | None | N | None | 0 | 1.66834E-05 | None | 0 | 0 | None | 1.56309E-05 | 0 | 2.28896E-05 | 1.09859E-05 | 9.6123E-05 |
| R/H | rs397517770 |
-2.711 | 1.0 | D | 0.781 | 0.556 | 0.490489133298 | gnomAD-2.1.1 | 1.73521E-04 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 5.62E-05 | None | 1.31113E-03 | None | 0 | 8.92E-06 | 0 |
| R/H | rs397517770 |
-2.711 | 1.0 | D | 0.781 | 0.556 | 0.490489133298 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.24481E-03 | 0 |
| R/H | rs397517770 |
-2.711 | 1.0 | D | 0.781 | 0.556 | 0.490489133298 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| R/H | rs397517770 |
-2.711 | 1.0 | D | 0.781 | 0.556 | 0.490489133298 | gnomAD-4.0.0 | 9.35973E-05 | None | None | None | None | N | None | 2.66596E-05 | 1.66795E-05 | None | 0 | 2.23534E-05 | None | 0 | 4.95213E-04 | 7.62978E-06 | 1.46144E-03 | 3.20266E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9925 | likely_pathogenic | 0.9894 | pathogenic | -2.006 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/C | 0.8713 | likely_pathogenic | 0.8151 | pathogenic | -1.847 | Destabilizing | 1.0 | D | 0.874 | deleterious | D | 0.531852706 | None | None | N |
| R/D | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -1.322 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| R/E | 0.9905 | likely_pathogenic | 0.9875 | pathogenic | -1.094 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/F | 0.998 | likely_pathogenic | 0.9971 | pathogenic | -0.985 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| R/G | 0.9903 | likely_pathogenic | 0.9857 | pathogenic | -2.337 | Highly Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.538093676 | None | None | N |
| R/H | 0.8268 | likely_pathogenic | 0.7626 | pathogenic | -1.945 | Destabilizing | 1.0 | D | 0.781 | deleterious | D | 0.549449982 | None | None | N |
| R/I | 0.9911 | likely_pathogenic | 0.9882 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| R/K | 0.814 | likely_pathogenic | 0.7762 | pathogenic | -1.215 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/L | 0.9788 | likely_pathogenic | 0.9703 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.513949034 | None | None | N |
| R/M | 0.9932 | likely_pathogenic | 0.9896 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/N | 0.9977 | likely_pathogenic | 0.9971 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.344 | Destabilizing | 1.0 | D | 0.838 | deleterious | D | 0.549703471 | None | None | N |
| R/Q | 0.7972 | likely_pathogenic | 0.715 | pathogenic | -1.259 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| R/S | 0.9952 | likely_pathogenic | 0.9928 | pathogenic | -2.268 | Highly Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.511213556 | None | None | N |
| R/T | 0.9953 | likely_pathogenic | 0.9933 | pathogenic | -1.839 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| R/V | 0.9909 | likely_pathogenic | 0.9877 | pathogenic | -1.344 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/W | 0.9631 | likely_pathogenic | 0.9431 | pathogenic | -0.582 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| R/Y | 0.9929 | likely_pathogenic | 0.9899 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.868 | 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.