Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17404 | 52435;52436;52437 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| N2AB | 15763 | 47512;47513;47514 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| N2A | 14836 | 44731;44732;44733 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| N2B | 8339 | 25240;25241;25242 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| Novex-1 | 8464 | 25615;25616;25617 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| Novex-2 | 8531 | 25816;25817;25818 | chr2:178608801;178608800;178608799 | chr2:179473528;179473527;179473526 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs2055555146  |
None | 1.0 | D | 0.859 | 0.882 | 0.887553138465 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs2055555146 |
None | 1.0 | D | 0.859 | 0.882 | 0.887553138465 | gnomAD-4.0.0 | 6.57834E-06 | None | None | None | None | I | None | 0 | 6.55652E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs754650111 |
-3.427 | 1.0 | D | 0.879 | 0.879 | 0.920531858431 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| Y/N | rs754650111 |
-3.427 | 1.0 | D | 0.879 | 0.879 | 0.920531858431 | gnomAD-4.0.0 | 1.36936E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79965E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9984 | likely_pathogenic | 0.9988 | pathogenic | -3.645 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| Y/C | 0.9656 | likely_pathogenic | 0.973 | pathogenic | -2.217 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.647922883 | None | None | I |
| Y/D | 0.9979 | likely_pathogenic | 0.9982 | pathogenic | -3.925 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.648326492 | None | None | I |
| Y/E | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.71 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| Y/F | 0.4926 | ambiguous | 0.5409 | ambiguous | -1.405 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | D | 0.564547208 | None | None | I |
| Y/G | 0.9946 | likely_pathogenic | 0.9952 | pathogenic | -4.055 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | I |
| Y/H | 0.9896 | likely_pathogenic | 0.992 | pathogenic | -2.67 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | D | 0.631671358 | None | None | I |
| Y/I | 0.9898 | likely_pathogenic | 0.9911 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| Y/K | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -2.541 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | I |
| Y/L | 0.9686 | likely_pathogenic | 0.97 | pathogenic | -2.251 | Highly Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | I |
| Y/M | 0.993 | likely_pathogenic | 0.994 | pathogenic | -2.057 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| Y/N | 0.9891 | likely_pathogenic | 0.9902 | pathogenic | -3.327 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.648326492 | None | None | I |
| Y/P | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -2.736 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | I |
| Y/Q | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -3.073 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| Y/R | 0.9969 | likely_pathogenic | 0.9972 | pathogenic | -2.26 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| Y/S | 0.9937 | likely_pathogenic | 0.9947 | pathogenic | -3.667 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.648326492 | None | None | I |
| Y/T | 0.9976 | likely_pathogenic | 0.998 | pathogenic | -3.332 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| Y/V | 0.9776 | likely_pathogenic | 0.9805 | pathogenic | -2.736 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | I |
| Y/W | 0.9295 | likely_pathogenic | 0.9392 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
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.