Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27773 | 83542;83543;83544 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| N2AB | 26132 | 78619;78620;78621 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| N2A | 25205 | 75838;75839;75840 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| N2B | 18708 | 56347;56348;56349 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| Novex-1 | 18833 | 56722;56723;56724 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| Novex-2 | 18900 | 56923;56924;56925 | chr2:178562815;178562814;178562813 | chr2:179427542;179427541;179427540 |
| 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 | rs767568495  |
-1.598 | 0.318 | N | 0.435 | 0.289 | 0.642644294093 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| L/F | rs767568495 |
-1.598 | 0.318 | N | 0.435 | 0.289 | 0.642644294093 | gnomAD-4.0.0 | 2.05368E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7994E-06 | 0 | 1.65826E-05 |
| L/M | None | None | 0.999 | N | 0.769 | 0.452 | 0.448597761117 | gnomAD-4.0.0 | 6.84508E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99659E-07 | 0 | 0 |
| L/V | rs376683928 |
None | 0.936 | N | 0.707 | 0.317 | 0.435043484731 | gnomAD-4.0.0 | 1.36902E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79932E-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 | 0.8913 | likely_pathogenic | 0.8884 | pathogenic | -2.398 | Highly Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| L/C | 0.7339 | likely_pathogenic | 0.7283 | pathogenic | -1.918 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| L/D | 0.9979 | likely_pathogenic | 0.9977 | pathogenic | -2.617 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/E | 0.99 | likely_pathogenic | 0.9885 | pathogenic | -2.477 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| L/F | 0.2272 | likely_benign | 0.224 | benign | -1.544 | Destabilizing | 0.318 | N | 0.435 | neutral | N | 0.48996829 | None | None | N |
| L/G | 0.9767 | likely_pathogenic | 0.9752 | pathogenic | -2.88 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/H | 0.9446 | likely_pathogenic | 0.9394 | pathogenic | -2.321 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/I | 0.1094 | likely_benign | 0.1122 | benign | -1.044 | Destabilizing | 0.936 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/K | 0.9735 | likely_pathogenic | 0.97 | pathogenic | -1.814 | Destabilizing | 0.997 | D | 0.842 | deleterious | None | None | None | None | N |
| L/M | 0.195 | likely_benign | 0.1952 | benign | -1.024 | Destabilizing | 0.999 | D | 0.769 | deleterious | N | 0.514517779 | None | None | N |
| L/N | 0.982 | likely_pathogenic | 0.9799 | pathogenic | -1.944 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/P | 0.9216 | likely_pathogenic | 0.9243 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/Q | 0.9479 | likely_pathogenic | 0.9399 | pathogenic | -1.944 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/R | 0.9547 | likely_pathogenic | 0.9487 | pathogenic | -1.425 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/S | 0.9761 | likely_pathogenic | 0.9743 | pathogenic | -2.626 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | D | 0.541522804 | None | None | N |
| L/T | 0.8564 | likely_pathogenic | 0.8507 | pathogenic | -2.349 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/V | 0.1219 | likely_benign | 0.1295 | benign | -1.472 | Destabilizing | 0.936 | D | 0.707 | prob.neutral | N | 0.508654171 | None | None | N |
| L/W | 0.8203 | likely_pathogenic | 0.8123 | pathogenic | -1.85 | Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.553386089 | None | None | N |
| L/Y | 0.838 | likely_pathogenic | 0.8216 | pathogenic | -1.592 | Destabilizing | 0.976 | D | 0.801 | 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.