Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27696 | 83311;83312;83313 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| N2AB | 26055 | 78388;78389;78390 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| N2A | 25128 | 75607;75608;75609 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| N2B | 18631 | 56116;56117;56118 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| Novex-1 | 18756 | 56491;56492;56493 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| Novex-2 | 18823 | 56692;56693;56694 | chr2:178563046;178563045;178563044 | chr2:179427773;179427772;179427771 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs769398545  |
-0.761 | 1.0 | N | 0.771 | 0.597 | 0.862818656922 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| F/C | rs769398545 |
-0.761 | 1.0 | N | 0.771 | 0.597 | 0.862818656922 | gnomAD-4.0.0 | 4.1055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.95604E-05 | 0 |
| F/S | rs769398545 |
-1.919 | 1.0 | N | 0.774 | 0.524 | 0.8144640112 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| F/S | rs769398545 |
-1.919 | 1.0 | N | 0.774 | 0.524 | 0.8144640112 | gnomAD-4.0.0 | 6.8425E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9118 | likely_pathogenic | 0.9057 | pathogenic | -1.924 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| F/C | 0.7714 | likely_pathogenic | 0.7908 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.494010895 | None | None | N |
| F/D | 0.9831 | likely_pathogenic | 0.9828 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| F/E | 0.9826 | likely_pathogenic | 0.9823 | pathogenic | -0.263 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| F/G | 0.9657 | likely_pathogenic | 0.9612 | pathogenic | -2.238 | Highly Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| F/H | 0.8235 | likely_pathogenic | 0.811 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| F/I | 0.8064 | likely_pathogenic | 0.8084 | pathogenic | -0.999 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.486755967 | None | None | N |
| F/K | 0.9738 | likely_pathogenic | 0.972 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| F/L | 0.9742 | likely_pathogenic | 0.9744 | pathogenic | -0.999 | Destabilizing | 0.999 | D | 0.525 | neutral | N | 0.492826288 | None | None | N |
| F/M | 0.8054 | likely_pathogenic | 0.8028 | pathogenic | -0.773 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| F/N | 0.9013 | likely_pathogenic | 0.9082 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| F/P | 0.9943 | likely_pathogenic | 0.9926 | pathogenic | -1.298 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| F/Q | 0.9354 | likely_pathogenic | 0.9313 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| F/R | 0.923 | likely_pathogenic | 0.9129 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| F/S | 0.8597 | likely_pathogenic | 0.8485 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.451035593 | None | None | N |
| F/T | 0.925 | likely_pathogenic | 0.9244 | pathogenic | -1.657 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| F/V | 0.7831 | likely_pathogenic | 0.7893 | pathogenic | -1.298 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.500715052 | None | None | N |
| F/W | 0.7844 | likely_pathogenic | 0.7591 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| F/Y | 0.3447 | ambiguous | 0.3417 | ambiguous | -0.476 | Destabilizing | 0.999 | D | 0.471 | neutral | N | 0.485534956 | 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.