Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19747 | 59464;59465;59466 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| N2AB | 18106 | 54541;54542;54543 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| N2A | 17179 | 51760;51761;51762 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| N2B | 10682 | 32269;32270;32271 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| Novex-1 | 10807 | 32644;32645;32646 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| Novex-2 | 10874 | 32845;32846;32847 | chr2:178592880;178592879;178592878 | chr2:179457607;179457606;179457605 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs369883019  |
-2.079 | 1.0 | D | 0.873 | 0.665 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| L/F | rs369883019 |
-2.079 | 1.0 | D | 0.873 | 0.665 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs369883019 |
-2.079 | 1.0 | D | 0.873 | 0.665 | None | gnomAD-4.0.0 | 2.47935E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.391E-06 | 0 | 0 |
| L/R | rs2154185954 |
None | 1.0 | D | 0.854 | 0.929 | 0.943940270598 | gnomAD-4.0.0 | 1.20047E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31267E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9669 | likely_pathogenic | 0.9598 | pathogenic | -2.525 | Highly Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | N |
| L/C | 0.945 | likely_pathogenic | 0.9309 | pathogenic | -2.109 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -2.296 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| L/E | 0.9955 | likely_pathogenic | 0.9944 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/F | 0.8785 | likely_pathogenic | 0.8494 | pathogenic | -1.598 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.6429206 | None | None | N |
| L/G | 0.9917 | likely_pathogenic | 0.9881 | pathogenic | -3.101 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/H | 0.9924 | likely_pathogenic | 0.9895 | pathogenic | -2.469 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | D | 0.669265928 | None | None | N |
| L/I | 0.378 | ambiguous | 0.3551 | ambiguous | -0.857 | Destabilizing | 0.999 | D | 0.839 | deleterious | D | 0.635178803 | None | None | N |
| L/K | 0.9894 | likely_pathogenic | 0.9862 | pathogenic | -1.837 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/M | 0.4716 | ambiguous | 0.4778 | ambiguous | -0.963 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/N | 0.9947 | likely_pathogenic | 0.9932 | pathogenic | -2.2 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/P | 0.992 | likely_pathogenic | 0.9902 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.856 | deleterious | D | 0.669265928 | None | None | N |
| L/Q | 0.9831 | likely_pathogenic | 0.9789 | pathogenic | -2.002 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/R | 0.9828 | likely_pathogenic | 0.9766 | pathogenic | -1.671 | Destabilizing | 1.0 | D | 0.854 | deleterious | D | 0.653246568 | None | None | N |
| L/S | 0.9955 | likely_pathogenic | 0.9941 | pathogenic | -3.033 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/T | 0.9793 | likely_pathogenic | 0.9724 | pathogenic | -2.607 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/V | 0.5026 | ambiguous | 0.4605 | ambiguous | -1.394 | Destabilizing | 0.999 | D | 0.849 | deleterious | D | 0.582588151 | None | None | N |
| L/W | 0.988 | likely_pathogenic | 0.9825 | pathogenic | -1.833 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| L/Y | 0.9904 | likely_pathogenic | 0.9878 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.831 | 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.