Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30743 | 92452;92453;92454 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| N2AB | 29102 | 87529;87530;87531 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| N2A | 28175 | 84748;84749;84750 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| N2B | 21678 | 65257;65258;65259 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| Novex-1 | 21803 | 65632;65633;65634 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| Novex-2 | 21870 | 65833;65834;65835 | chr2:178549399;178549398;178549397 | chr2:179414126;179414125;179414124 |
| 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/R | rs771621337  |
-0.906 | 1.0 | D | 0.908 | 0.731 | 0.829251667788 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| P/R | rs771621337 |
-0.906 | 1.0 | D | 0.908 | 0.731 | 0.829251667788 | gnomAD-4.0.0 | 3.18291E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41313E-04 | 2.85843E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9365 | likely_pathogenic | 0.9324 | pathogenic | -1.989 | Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.598312882 | None | None | N |
| P/C | 0.9944 | likely_pathogenic | 0.994 | pathogenic | -1.426 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| P/D | 0.999 | likely_pathogenic | 0.9991 | pathogenic | -2.014 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| P/E | 0.9976 | likely_pathogenic | 0.9976 | pathogenic | -1.986 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| P/F | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| P/G | 0.9907 | likely_pathogenic | 0.9901 | pathogenic | -2.361 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/H | 0.9968 | likely_pathogenic | 0.9971 | pathogenic | -1.89 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| P/I | 0.9963 | likely_pathogenic | 0.9964 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| P/K | 0.9982 | likely_pathogenic | 0.9983 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| P/L | 0.9793 | likely_pathogenic | 0.9782 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.921 | deleterious | D | 0.63969891 | None | None | N |
| P/M | 0.9968 | likely_pathogenic | 0.997 | pathogenic | -0.756 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/N | 0.9986 | likely_pathogenic | 0.9987 | pathogenic | -1.535 | Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| P/Q | 0.9957 | likely_pathogenic | 0.9958 | pathogenic | -1.687 | Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.640707932 | None | None | N |
| P/R | 0.995 | likely_pathogenic | 0.9948 | pathogenic | -1.164 | Destabilizing | 1.0 | D | 0.908 | deleterious | D | 0.640506128 | None | None | N |
| P/S | 0.9851 | likely_pathogenic | 0.9865 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.578407442 | None | None | N |
| P/T | 0.979 | likely_pathogenic | 0.9797 | pathogenic | -1.935 | Destabilizing | 1.0 | D | 0.888 | deleterious | D | 0.617320023 | None | None | N |
| P/V | 0.9882 | likely_pathogenic | 0.9881 | pathogenic | -1.321 | Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| P/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.78 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| P/Y | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.53 | Destabilizing | 1.0 | D | 0.915 | 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.