Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32836 | 98731;98732;98733 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| N2AB | 31195 | 93808;93809;93810 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| N2A | 30268 | 91027;91028;91029 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| N2B | 23771 | 71536;71537;71538 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| Novex-1 | 23896 | 71911;71912;71913 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| Novex-2 | 23963 | 72112;72113;72114 | chr2:178539559;178539558;178539557 | chr2:179404286;179404285;179404284 |
| 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 | rs368312810  |
-1.034 | 1.0 | N | 0.679 | 0.409 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/Q | rs368312810 |
-1.034 | 1.0 | N | 0.679 | 0.409 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs368312810 |
-1.034 | 1.0 | N | 0.679 | 0.409 | None | gnomAD-4.0.0 | 1.11546E-05 | None | None | None | None | N | None | 2.67108E-05 | 0 | None | 0 | 2.22816E-05 | None | 0 | 1.64474E-04 | 1.01712E-05 | 2.19558E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9485 | likely_pathogenic | 0.8859 | pathogenic | -1.888 | Destabilizing | 0.999 | D | 0.538 | neutral | None | None | None | None | N |
| R/C | 0.553 | ambiguous | 0.38 | ambiguous | -1.77 | Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| R/D | 0.9948 | likely_pathogenic | 0.9874 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/E | 0.9085 | likely_pathogenic | 0.8226 | pathogenic | -0.784 | Destabilizing | 0.999 | D | 0.545 | neutral | None | None | None | None | N |
| R/F | 0.9544 | likely_pathogenic | 0.9201 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| R/G | 0.9216 | likely_pathogenic | 0.8254 | pathogenic | -2.259 | Highly Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.493667003 | None | None | N |
| R/H | 0.5183 | ambiguous | 0.3788 | ambiguous | -1.971 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/I | 0.9185 | likely_pathogenic | 0.8241 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.922 | deleterious | None | None | None | None | N |
| R/K | 0.3153 | likely_benign | 0.2281 | benign | -1.241 | Destabilizing | 0.998 | D | 0.48 | neutral | None | None | None | None | N |
| R/L | 0.8277 | likely_pathogenic | 0.6958 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.484018991 | None | None | N |
| R/M | 0.8458 | likely_pathogenic | 0.7004 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| R/N | 0.9824 | likely_pathogenic | 0.9617 | pathogenic | -1.386 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/P | 0.9971 | likely_pathogenic | 0.9936 | pathogenic | -1.158 | Destabilizing | 1.0 | D | 0.9 | deleterious | N | 0.51531643 | None | None | N |
| R/Q | 0.3077 | likely_benign | 0.1936 | benign | -1.179 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.473014626 | None | None | N |
| R/S | 0.9722 | likely_pathogenic | 0.9334 | pathogenic | -2.232 | Highly Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| R/T | 0.9386 | likely_pathogenic | 0.8462 | pathogenic | -1.778 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| R/V | 0.9249 | likely_pathogenic | 0.8436 | pathogenic | -1.158 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| R/W | 0.6835 | likely_pathogenic | 0.5466 | ambiguous | -0.473 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/Y | 0.8889 | likely_pathogenic | 0.8207 | pathogenic | -0.351 | Destabilizing | 1.0 | D | 0.921 | 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.