Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18858 | 56797;56798;56799 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| N2AB | 17217 | 51874;51875;51876 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| N2A | 16290 | 49093;49094;49095 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| N2B | 9793 | 29602;29603;29604 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| Novex-1 | 9918 | 29977;29978;29979 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| Novex-2 | 9985 | 30178;30179;30180 | chr2:178599221;178599220;178599219 | chr2:179463948;179463947;179463946 |
| 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/Q | rs755848019  |
-1.124 | 0.929 | N | 0.569 | 0.411 | 0.369682402691 | gnomAD-2.1.1 | 5.42E-05 | None | None | None | None | N | None | 6.96E-05 | 0 | None | 0 | 0 | None | 6.14E-05 | None | 0 | 8.92E-05 | 0 |
| R/Q | rs755848019 |
-1.124 | 0.929 | N | 0.569 | 0.411 | 0.369682402691 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs755848019 |
-1.124 | 0.929 | N | 0.569 | 0.411 | 0.369682402691 | gnomAD-4.0.0 | 6.93293E-05 | None | None | None | None | N | None | 4.17269E-05 | 2.17628E-05 | None | 0 | 2.28843E-05 | None | 0 | 0 | 7.78706E-05 | 1.36556E-04 | 3.39709E-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 | 0.9923 | likely_pathogenic | 0.9879 | pathogenic | -1.516 | Destabilizing | 0.754 | D | 0.595 | neutral | None | None | None | None | N |
| R/C | 0.724 | likely_pathogenic | 0.6101 | pathogenic | -1.51 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/D | 0.9986 | likely_pathogenic | 0.9984 | pathogenic | -0.857 | Destabilizing | 0.754 | D | 0.625 | neutral | None | None | None | None | N |
| R/E | 0.9784 | likely_pathogenic | 0.9695 | pathogenic | -0.636 | Destabilizing | 0.019 | N | 0.467 | neutral | None | None | None | None | N |
| R/F | 0.9964 | likely_pathogenic | 0.9949 | pathogenic | -0.61 | Destabilizing | 0.993 | D | 0.743 | deleterious | None | None | None | None | N |
| R/G | 0.9839 | likely_pathogenic | 0.9756 | pathogenic | -1.89 | Destabilizing | 0.922 | D | 0.625 | neutral | D | 0.533904892 | None | None | N |
| R/H | 0.5842 | likely_pathogenic | 0.4528 | ambiguous | -1.752 | Destabilizing | 0.978 | D | 0.591 | neutral | None | None | None | None | N |
| R/I | 0.9867 | likely_pathogenic | 0.979 | pathogenic | -0.443 | Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/K | 0.6265 | likely_pathogenic | 0.5003 | ambiguous | -1.183 | Destabilizing | 0.559 | D | 0.648 | neutral | None | None | None | None | N |
| R/L | 0.9731 | likely_pathogenic | 0.9575 | pathogenic | -0.443 | Destabilizing | 0.976 | D | 0.629 | neutral | N | 0.513585364 | None | None | N |
| R/M | 0.9868 | likely_pathogenic | 0.9758 | pathogenic | -0.971 | Destabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | N |
| R/N | 0.9945 | likely_pathogenic | 0.9926 | pathogenic | -1.254 | Destabilizing | 0.956 | D | 0.547 | neutral | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -0.787 | Destabilizing | 0.988 | D | 0.691 | prob.neutral | D | 0.54593276 | None | None | N |
| R/Q | 0.6004 | likely_pathogenic | 0.452 | ambiguous | -1.037 | Destabilizing | 0.929 | D | 0.569 | neutral | N | 0.489743437 | None | None | N |
| R/S | 0.9911 | likely_pathogenic | 0.9875 | pathogenic | -1.999 | Destabilizing | 0.754 | D | 0.565 | neutral | None | None | None | None | N |
| R/T | 0.9897 | likely_pathogenic | 0.982 | pathogenic | -1.565 | Destabilizing | 0.956 | D | 0.569 | neutral | None | None | None | None | N |
| R/V | 0.9886 | likely_pathogenic | 0.983 | pathogenic | -0.787 | Destabilizing | 0.956 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/W | 0.9241 | likely_pathogenic | 0.8881 | pathogenic | -0.213 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9853 | likely_pathogenic | 0.9773 | pathogenic | -0.046 | Destabilizing | 0.993 | D | 0.716 | 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.