Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26223 | 78892;78893;78894 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| N2AB | 24582 | 73969;73970;73971 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| N2A | 23655 | 71188;71189;71190 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| N2B | 17158 | 51697;51698;51699 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| Novex-1 | 17283 | 52072;52073;52074 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| Novex-2 | 17350 | 52273;52274;52275 | chr2:178567465;178567464;178567463 | chr2:179432192;179432191;179432190 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs1706322297  |
None | 1.0 | D | 0.834 | 0.775 | 0.672866344077 | gnomAD-4.0.0 | 1.59279E-06 | None | None | None | None | N | None | 5.66636E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs777105534 |
-2.348 | 1.0 | D | 0.853 | 0.788 | 0.594734989949 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.71E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs777105534 |
-2.348 | 1.0 | D | 0.853 | 0.788 | 0.594734989949 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs777105534 |
-2.348 | 1.0 | D | 0.853 | 0.788 | 0.594734989949 | gnomAD-4.0.0 | 6.81938E-06 | None | None | None | None | N | None | 0 | 6.67401E-05 | None | 0 | 0 | None | 0 | 0 | 5.08689E-06 | 1.09917E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9384 | likely_pathogenic | 0.9394 | pathogenic | -1.345 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.531600028 | None | None | N |
| P/C | 0.9939 | likely_pathogenic | 0.9938 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| P/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.078 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| P/E | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| P/F | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| P/G | 0.9958 | likely_pathogenic | 0.9959 | pathogenic | -1.599 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| P/H | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -1.174 | Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.565873208 | None | None | N |
| P/I | 0.9918 | likely_pathogenic | 0.9927 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| P/K | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -0.937 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| P/L | 0.9708 | likely_pathogenic | 0.9674 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.549447113 | None | None | N |
| P/M | 0.9963 | likely_pathogenic | 0.9962 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| P/N | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| P/Q | 0.9977 | likely_pathogenic | 0.9978 | pathogenic | -0.964 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| P/R | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.583470484 | None | None | N |
| P/S | 0.9941 | likely_pathogenic | 0.9942 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.56485925 | None | None | N |
| P/T | 0.9899 | likely_pathogenic | 0.9907 | pathogenic | -1.178 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.5716072 | None | None | N |
| P/V | 0.9794 | likely_pathogenic | 0.9806 | pathogenic | -0.924 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| P/W | 0.9999 | likely_pathogenic | 0.9998 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| P/Y | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.089 | Destabilizing | 1.0 | D | 0.867 | 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.