Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27013 | 81262;81263;81264 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| N2AB | 25372 | 76339;76340;76341 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| N2A | 24445 | 73558;73559;73560 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| N2B | 17948 | 54067;54068;54069 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| Novex-1 | 18073 | 54442;54443;54444 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| Novex-2 | 18140 | 54643;54644;54645 | chr2:178565095;178565094;178565093 | chr2:179429822;179429821;179429820 |
| 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/L | rs376374751  |
-1.124 | 0.922 | N | 0.614 | 0.445 | 0.48300943003 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs376374751 |
-1.124 | 0.922 | N | 0.614 | 0.445 | 0.48300943003 | gnomAD-4.0.0 | 6.84288E-07 | None | None | None | None | N | None | 2.989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs376374751 |
-1.349 | 0.447 | N | 0.33 | 0.298 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 9.68E-05 | 0 | None | 0 | None | 4E-05 | 9.39E-05 | 0 |
| R/Q | rs376374751 |
-1.349 | 0.447 | N | 0.33 | 0.298 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| R/Q | rs376374751 |
-1.349 | 0.447 | N | 0.33 | 0.298 | None | gnomAD-4.0.0 | 4.52448E-05 | None | None | None | None | N | None | 8.01496E-05 | 1.66767E-05 | None | 0 | 0 | None | 1.56216E-05 | 4.93746E-04 | 4.91663E-05 | 0 | 6.40512E-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 | 0.9846 | likely_pathogenic | 0.9821 | pathogenic | -1.704 | Destabilizing | 0.86 | D | 0.587 | neutral | None | None | None | None | N |
| R/C | 0.7137 | likely_pathogenic | 0.674 | pathogenic | -1.865 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| R/D | 0.9984 | likely_pathogenic | 0.9982 | pathogenic | -1.171 | Destabilizing | 0.956 | D | 0.656 | neutral | None | None | None | None | N |
| R/E | 0.9779 | likely_pathogenic | 0.9756 | pathogenic | -1.0 | Destabilizing | 0.754 | D | 0.54 | neutral | None | None | None | None | N |
| R/F | 0.9925 | likely_pathogenic | 0.9931 | pathogenic | -1.304 | Destabilizing | 0.993 | D | 0.781 | deleterious | None | None | None | None | N |
| R/G | 0.972 | likely_pathogenic | 0.9709 | pathogenic | -1.983 | Destabilizing | 0.922 | D | 0.614 | neutral | N | 0.502225378 | None | None | N |
| R/H | 0.7507 | likely_pathogenic | 0.7448 | pathogenic | -1.984 | Destabilizing | 0.978 | D | 0.519 | neutral | None | None | None | None | N |
| R/I | 0.977 | likely_pathogenic | 0.9753 | pathogenic | -0.914 | Destabilizing | 0.978 | D | 0.784 | deleterious | None | None | None | None | N |
| R/K | 0.4802 | ambiguous | 0.5061 | ambiguous | -1.364 | Destabilizing | 0.076 | N | 0.216 | neutral | None | None | None | None | N |
| R/L | 0.9496 | likely_pathogenic | 0.9477 | pathogenic | -0.914 | Destabilizing | 0.922 | D | 0.614 | neutral | N | 0.499654484 | None | None | N |
| R/M | 0.9518 | likely_pathogenic | 0.9539 | pathogenic | -1.36 | Destabilizing | 0.994 | D | 0.666 | neutral | None | None | None | None | N |
| R/N | 0.9929 | likely_pathogenic | 0.9912 | pathogenic | -1.263 | Destabilizing | 0.86 | D | 0.461 | neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.165 | Destabilizing | 0.988 | D | 0.72 | prob.delet. | N | 0.518772697 | None | None | N |
| R/Q | 0.6212 | likely_pathogenic | 0.601 | pathogenic | -1.198 | Destabilizing | 0.447 | N | 0.33 | neutral | N | 0.476964645 | None | None | N |
| R/S | 0.9941 | likely_pathogenic | 0.9924 | pathogenic | -1.992 | Destabilizing | 0.86 | D | 0.539 | neutral | None | None | None | None | N |
| R/T | 0.9866 | likely_pathogenic | 0.9839 | pathogenic | -1.641 | Destabilizing | 0.86 | D | 0.559 | neutral | None | None | None | None | N |
| R/V | 0.9813 | likely_pathogenic | 0.9777 | pathogenic | -1.165 | Destabilizing | 0.956 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/W | 0.9246 | likely_pathogenic | 0.933 | pathogenic | -1.015 | Destabilizing | 0.998 | D | 0.752 | deleterious | None | None | None | None | N |
| R/Y | 0.9721 | likely_pathogenic | 0.9723 | pathogenic | -0.738 | Destabilizing | 0.993 | D | 0.741 | 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.