Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19258 | 57997;57998;57999 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| N2AB | 17617 | 53074;53075;53076 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| N2A | 16690 | 50293;50294;50295 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| N2B | 10193 | 30802;30803;30804 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| Novex-1 | 10318 | 31177;31178;31179 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| Novex-2 | 10385 | 31378;31379;31380 | chr2:178595582;178595581;178595580 | chr2:179460309;179460308;179460307 |
| 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/F | rs1467911072  |
-1.963 | 0.982 | N | 0.587 | 0.498 | 0.563873649602 | gnomAD-2.1.1 | 1.51E-05 | None | None | None | None | N | None | 0 | 1.03605E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs1467911072 |
-1.963 | 0.982 | N | 0.587 | 0.498 | 0.563873649602 | gnomAD-4.0.0 | 5.03846E-06 | None | None | None | None | N | None | 0 | 7.71446E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | None | None | 0.58 | N | 0.251 | 0.126 | 0.419713421852 | gnomAD-4.0.0 | 1.67949E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.01383E-06 | 0 | 0 |
| I/T | rs1360164741 |
-3.438 | 0.939 | N | 0.699 | 0.486 | 0.6965871858 | gnomAD-2.1.1 | 5.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.19E-05 | 0 |
| I/T | rs1360164741 |
-3.438 | 0.939 | N | 0.699 | 0.486 | 0.6965871858 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.31079E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| I/T | rs1360164741 |
-3.438 | 0.939 | N | 0.699 | 0.486 | 0.6965871858 | gnomAD-4.0.0 | 5.06282E-06 | None | None | None | None | N | None | 0 | 3.63082E-05 | None | 0 | 0 | None | 0 | 0 | 2.58297E-06 | 0 | 4.89412E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7741 | likely_pathogenic | 0.8174 | pathogenic | -2.752 | Highly Destabilizing | 0.91 | D | 0.624 | neutral | None | None | None | None | N |
| I/C | 0.9016 | likely_pathogenic | 0.9175 | pathogenic | -1.724 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/D | 0.9986 | likely_pathogenic | 0.9989 | pathogenic | -3.301 | Highly Destabilizing | 0.998 | D | 0.885 | deleterious | None | None | None | None | N |
| I/E | 0.9953 | likely_pathogenic | 0.9958 | pathogenic | -3.02 | Highly Destabilizing | 0.993 | D | 0.881 | deleterious | None | None | None | None | N |
| I/F | 0.7822 | likely_pathogenic | 0.8343 | pathogenic | -1.688 | Destabilizing | 0.982 | D | 0.587 | neutral | N | 0.497456119 | None | None | N |
| I/G | 0.9819 | likely_pathogenic | 0.9854 | pathogenic | -3.251 | Highly Destabilizing | 0.993 | D | 0.875 | deleterious | None | None | None | None | N |
| I/H | 0.9956 | likely_pathogenic | 0.9965 | pathogenic | -2.875 | Highly Destabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | N |
| I/K | 0.9906 | likely_pathogenic | 0.9927 | pathogenic | -2.203 | Highly Destabilizing | 0.993 | D | 0.881 | deleterious | None | None | None | None | N |
| I/L | 0.3139 | likely_benign | 0.3627 | ambiguous | -1.221 | Destabilizing | 0.58 | D | 0.251 | neutral | N | 0.482272859 | None | None | N |
| I/M | 0.324 | likely_benign | 0.3604 | ambiguous | -1.401 | Destabilizing | 0.991 | D | 0.621 | neutral | D | 0.522660831 | None | None | N |
| I/N | 0.9829 | likely_pathogenic | 0.9871 | pathogenic | -2.926 | Highly Destabilizing | 0.997 | D | 0.9 | deleterious | N | 0.498216588 | None | None | N |
| I/P | 0.9948 | likely_pathogenic | 0.9957 | pathogenic | -1.729 | Destabilizing | 0.998 | D | 0.899 | deleterious | None | None | None | None | N |
| I/Q | 0.9918 | likely_pathogenic | 0.9928 | pathogenic | -2.573 | Highly Destabilizing | 0.998 | D | 0.903 | deleterious | None | None | None | None | N |
| I/R | 0.9856 | likely_pathogenic | 0.9893 | pathogenic | -2.309 | Highly Destabilizing | 0.993 | D | 0.902 | deleterious | None | None | None | None | N |
| I/S | 0.945 | likely_pathogenic | 0.9592 | pathogenic | -3.274 | Highly Destabilizing | 0.991 | D | 0.829 | deleterious | N | 0.486860282 | None | None | N |
| I/T | 0.7828 | likely_pathogenic | 0.8406 | pathogenic | -2.855 | Highly Destabilizing | 0.939 | D | 0.699 | prob.neutral | N | 0.479858843 | None | None | N |
| I/V | 0.0868 | likely_benign | 0.0944 | benign | -1.729 | Destabilizing | 0.02 | N | 0.203 | neutral | N | 0.341626601 | None | None | N |
| I/W | 0.9945 | likely_pathogenic | 0.9959 | pathogenic | -1.878 | Destabilizing | 0.999 | D | 0.832 | deleterious | None | None | None | None | N |
| I/Y | 0.9805 | likely_pathogenic | 0.9859 | pathogenic | -1.857 | Destabilizing | 0.993 | D | 0.731 | prob.delet. | 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.