Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16469 | 49630;49631;49632 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| N2AB | 14828 | 44707;44708;44709 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| N2A | 13901 | 41926;41927;41928 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| N2B | 7404 | 22435;22436;22437 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| Novex-1 | 7529 | 22810;22811;22812 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| Novex-2 | 7596 | 23011;23012;23013 | chr2:178613878;178613877;178613876 | chr2:179478605;179478604;179478603 |
| 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/H | rs72677245  |
-3.29 | 1.0 | D | 0.902 | 0.665 | None | gnomAD-2.1.1 | 3.13247E-04 | None | None | None | None | N | None | 0 | 2.49027E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/H | rs72677245 |
-3.29 | 1.0 | D | 0.902 | 0.665 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 5.90319E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/H | rs72677245 |
-3.29 | 1.0 | D | 0.902 | 0.665 | None | gnomAD-4.0.0 | 1.33659E-04 | None | None | None | None | N | None | 0 | 1.75463E-03 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.85225E-05 |
| L/P | None | None | 1.0 | D | 0.936 | 0.753 | 0.874954315256 | gnomAD-4.0.0 | 1.59711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86697E-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 | 0.9692 | likely_pathogenic | 0.9679 | pathogenic | -2.64 | Highly Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/C | 0.9458 | likely_pathogenic | 0.9469 | pathogenic | -1.73 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/D | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.239 | Highly Destabilizing | 1.0 | D | 0.932 | deleterious | None | None | None | None | N |
| L/E | 0.9987 | likely_pathogenic | 0.9987 | pathogenic | -2.894 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| L/F | 0.8232 | likely_pathogenic | 0.8519 | pathogenic | -1.526 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.716699239 | None | None | N |
| L/G | 0.9976 | likely_pathogenic | 0.9974 | pathogenic | -3.272 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| L/H | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -3.097 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | D | 0.777126809 | None | None | N |
| L/I | 0.1766 | likely_benign | 0.1934 | benign | -0.724 | Destabilizing | 0.999 | D | 0.545 | neutral | N | 0.493343209 | None | None | N |
| L/K | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -1.845 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/M | 0.3713 | ambiguous | 0.3984 | ambiguous | -0.98 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/N | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -2.621 | Highly Destabilizing | 1.0 | D | 0.935 | deleterious | None | None | None | None | N |
| L/P | 0.999 | likely_pathogenic | 0.9991 | pathogenic | -1.356 | Destabilizing | 1.0 | D | 0.936 | deleterious | D | 0.777126809 | None | None | N |
| L/Q | 0.9965 | likely_pathogenic | 0.9966 | pathogenic | -2.188 | Highly Destabilizing | 1.0 | D | 0.931 | deleterious | None | None | None | None | N |
| L/R | 0.9971 | likely_pathogenic | 0.9973 | pathogenic | -2.103 | Highly Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.777126809 | None | None | N |
| L/S | 0.9976 | likely_pathogenic | 0.9978 | pathogenic | -3.138 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/T | 0.9862 | likely_pathogenic | 0.9864 | pathogenic | -2.616 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/V | 0.2153 | likely_benign | 0.2219 | benign | -1.356 | Destabilizing | 0.999 | D | 0.558 | neutral | N | 0.486839292 | None | None | N |
| L/W | 0.9933 | likely_pathogenic | 0.9953 | pathogenic | -1.885 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/Y | 0.9918 | likely_pathogenic | 0.993 | pathogenic | -1.707 | Destabilizing | 1.0 | D | 0.85 | 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.