Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27680 | 83263;83264;83265 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| N2AB | 26039 | 78340;78341;78342 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| N2A | 25112 | 75559;75560;75561 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| N2B | 18615 | 56068;56069;56070 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| Novex-1 | 18740 | 56443;56444;56445 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| Novex-2 | 18807 | 56644;56645;56646 | chr2:178563094;178563093;178563092 | chr2:179427821;179427820;179427819 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 0.919 | N | 0.653 | 0.355 | 0.461058313273 | gnomAD-4.0.0 | 1.59136E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| D/E | rs754885118  |
0.001 | 0.958 | N | 0.533 | 0.233 | 0.199424873507 | gnomAD-2.1.1 | 7.85E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12751E-03 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs754885118 |
0.001 | 0.958 | N | 0.533 | 0.233 | 0.199424873507 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.86548E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs754885118 |
0.001 | 0.958 | N | 0.533 | 0.233 | 0.199424873507 | gnomAD-4.0.0 | 6.81694E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22856E-04 | None | 0 | 0 | 0 | 0 | 1.60123E-05 |
| D/G | rs1431056112 |
-0.298 | 0.919 | N | 0.675 | 0.364 | 0.303781844768 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| D/G | rs1431056112 |
-0.298 | 0.919 | N | 0.675 | 0.364 | 0.303781844768 | gnomAD-4.0.0 | 6.36543E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.82625E-04 | 2.85874E-06 | 0 | 3.02462E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4651 | ambiguous | 0.3865 | ambiguous | -0.325 | Destabilizing | 0.919 | D | 0.653 | neutral | N | 0.480646424 | None | None | N |
| D/C | 0.9336 | likely_pathogenic | 0.9006 | pathogenic | -0.043 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| D/E | 0.2242 | likely_benign | 0.2183 | benign | -0.338 | Destabilizing | 0.958 | D | 0.533 | neutral | N | 0.450227517 | None | None | N |
| D/F | 0.9153 | likely_pathogenic | 0.8885 | pathogenic | -0.155 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| D/G | 0.5396 | ambiguous | 0.4559 | ambiguous | -0.566 | Destabilizing | 0.919 | D | 0.675 | prob.neutral | N | 0.520223533 | None | None | N |
| D/H | 0.7589 | likely_pathogenic | 0.6419 | pathogenic | -0.127 | Destabilizing | 0.999 | D | 0.749 | deleterious | N | 0.492414279 | None | None | N |
| D/I | 0.8203 | likely_pathogenic | 0.7466 | pathogenic | 0.275 | Stabilizing | 0.995 | D | 0.796 | deleterious | None | None | None | None | N |
| D/K | 0.8469 | likely_pathogenic | 0.7821 | pathogenic | 0.067 | Stabilizing | 0.991 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/L | 0.8057 | likely_pathogenic | 0.7398 | pathogenic | 0.275 | Stabilizing | 0.991 | D | 0.792 | deleterious | None | None | None | None | N |
| D/M | 0.9051 | likely_pathogenic | 0.8661 | pathogenic | 0.456 | Stabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| D/N | 0.2868 | likely_benign | 0.2009 | benign | -0.234 | Destabilizing | 0.958 | D | 0.675 | prob.neutral | N | 0.480044016 | None | None | N |
| D/P | 0.9531 | likely_pathogenic | 0.928 | pathogenic | 0.099 | Stabilizing | 0.995 | D | 0.767 | deleterious | None | None | None | None | N |
| D/Q | 0.7431 | likely_pathogenic | 0.6602 | pathogenic | -0.168 | Destabilizing | 0.991 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/R | 0.8778 | likely_pathogenic | 0.825 | pathogenic | 0.271 | Stabilizing | 0.991 | D | 0.767 | deleterious | None | None | None | None | N |
| D/S | 0.3176 | likely_benign | 0.244 | benign | -0.383 | Destabilizing | 0.484 | N | 0.394 | neutral | None | None | None | None | N |
| D/T | 0.5977 | likely_pathogenic | 0.5019 | ambiguous | -0.196 | Destabilizing | 0.982 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/V | 0.6083 | likely_pathogenic | 0.5032 | ambiguous | 0.099 | Stabilizing | 0.988 | D | 0.793 | deleterious | N | 0.48541284 | None | None | N |
| D/W | 0.9851 | likely_pathogenic | 0.9791 | pathogenic | -0.013 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/Y | 0.6777 | likely_pathogenic | 0.5774 | pathogenic | 0.074 | Stabilizing | 0.999 | D | 0.796 | deleterious | N | 0.503263606 | 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.