Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1305 | 4138;4139;4140 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| N2AB | 1305 | 4138;4139;4140 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| N2A | 1305 | 4138;4139;4140 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| N2B | 1259 | 4000;4001;4002 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| Novex-1 | 1259 | 4000;4001;4002 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| Novex-2 | 1259 | 4000;4001;4002 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
| Novex-3 | 1305 | 4138;4139;4140 | chr2:178779279;178779278;178779277 | chr2:179644006;179644005;179644004 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | rs1357320718  |
-0.419 | 1.0 | D | 0.785 | 0.775 | 0.668480267452 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| G/A | rs1357320718 |
-0.419 | 1.0 | D | 0.785 | 0.775 | 0.668480267452 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85724E-06 | 0 | 0 |
| G/E | None | None | 1.0 | D | 0.841 | 0.786 | 0.879687484539 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| G/R | rs199889888 |
-0.545 | 1.0 | D | 0.86 | 0.826 | 0.904080593739 | gnomAD-2.1.1 | 5.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.63E-05 | 9.75E-05 | 1.6442E-04 |
| G/R | rs199889888 |
-0.545 | 1.0 | D | 0.86 | 0.826 | 0.904080593739 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.77555E-04 |
| G/R | rs199889888 |
-0.545 | 1.0 | D | 0.86 | 0.826 | 0.904080593739 | gnomAD-4.0.0 | 2.41677E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.68794E-05 | 0 | 2.28846E-05 | 0 | 1.44051E-04 |
| G/W | rs199889888 |
-1.154 | 1.0 | D | 0.834 | 0.866 | None | gnomAD-2.1.1 | 6.04E-05 | None | None | None | None | N | None | 0 | 5.65E-05 | None | 0 | 0 | None | 0 | None | 7.97E-05 | 9.35E-05 | 1.39509E-04 |
| G/W | rs199889888 |
-1.154 | 1.0 | D | 0.834 | 0.866 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| G/W | rs199889888 |
-1.154 | 1.0 | D | 0.834 | 0.866 | None | gnomAD-4.0.0 | 4.02795E-05 | None | None | None | None | N | None | 0 | 5.0015E-05 | None | 0 | 0 | None | 1.56265E-05 | 4.93583E-04 | 4.49216E-05 | 0 | 8.00282E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.7365 | likely_pathogenic | 0.7971 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.785 | deleterious | D | 0.686613607 | None | None | N |
| G/C | 0.9191 | likely_pathogenic | 0.93 | pathogenic | -0.919 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| G/D | 0.7287 | likely_pathogenic | 0.7859 | pathogenic | -0.704 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| G/E | 0.8323 | likely_pathogenic | 0.8783 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.670435237 | None | None | N |
| G/F | 0.984 | likely_pathogenic | 0.988 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| G/H | 0.9323 | likely_pathogenic | 0.9532 | pathogenic | -0.597 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| G/I | 0.9811 | likely_pathogenic | 0.9855 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| G/K | 0.9473 | likely_pathogenic | 0.9597 | pathogenic | -1.032 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| G/L | 0.9708 | likely_pathogenic | 0.9791 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| G/M | 0.9711 | likely_pathogenic | 0.9796 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| G/N | 0.6588 | likely_pathogenic | 0.7433 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| G/P | 0.9969 | likely_pathogenic | 0.9978 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| G/Q | 0.8898 | likely_pathogenic | 0.9236 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| G/R | 0.9199 | likely_pathogenic | 0.9796 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.86 | deleterious | D | 0.750633175 | None | None | N |
| G/S | 0.471 | ambiguous | 0.5644 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| G/T | 0.836 | likely_pathogenic | 0.8831 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| G/V | 0.9547 | likely_pathogenic | 0.9645 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.75029759 | None | None | N |
| G/W | 0.9701 | likely_pathogenic | 0.9755 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.805148408 | None | None | N |
| G/Y | 0.955 | likely_pathogenic | 0.9651 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.838 | 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.