Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32823 | 98692;98693;98694 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| N2AB | 31182 | 93769;93770;93771 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| N2A | 30255 | 90988;90989;90990 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| N2B | 23758 | 71497;71498;71499 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| Novex-1 | 23883 | 71872;71873;71874 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| Novex-2 | 23950 | 72073;72074;72075 | chr2:178539598;178539597;178539596 | chr2:179404325;179404324;179404323 |
| 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/N | rs1365292715  |
0.011 | 1.0 | N | 0.744 | 0.388 | 0.393927044628 | 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 |
| D/N | rs1365292715 |
0.011 | 1.0 | N | 0.744 | 0.388 | 0.393927044628 | gnomAD-4.0.0 | 3.18222E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86541E-05 | 0 |
| D/V | None | None | 1.0 | N | 0.778 | 0.616 | 0.635702982859 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7678 | likely_pathogenic | 0.7508 | pathogenic | 0.098 | Stabilizing | 1.0 | D | 0.773 | deleterious | N | 0.495855822 | None | None | N |
| D/C | 0.9609 | likely_pathogenic | 0.9544 | pathogenic | 0.27 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| D/E | 0.7569 | likely_pathogenic | 0.7626 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.444 | neutral | N | 0.48990434 | None | None | N |
| D/F | 0.9746 | likely_pathogenic | 0.9712 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| D/G | 0.7505 | likely_pathogenic | 0.7221 | pathogenic | -0.159 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.5125185 | None | None | N |
| D/H | 0.8367 | likely_pathogenic | 0.8245 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.500401726 | None | None | N |
| D/I | 0.9398 | likely_pathogenic | 0.9328 | pathogenic | 0.727 | Stabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| D/K | 0.9308 | likely_pathogenic | 0.9235 | pathogenic | 0.029 | Stabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| D/L | 0.933 | likely_pathogenic | 0.924 | pathogenic | 0.727 | Stabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| D/M | 0.9748 | likely_pathogenic | 0.971 | pathogenic | 1.115 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/N | 0.1773 | likely_benign | 0.1763 | benign | -0.141 | Destabilizing | 1.0 | D | 0.744 | deleterious | N | 0.516038716 | None | None | N |
| D/P | 0.96 | likely_pathogenic | 0.951 | pathogenic | 0.543 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| D/Q | 0.9225 | likely_pathogenic | 0.919 | pathogenic | -0.061 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/R | 0.9327 | likely_pathogenic | 0.9263 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| D/S | 0.4457 | ambiguous | 0.4211 | ambiguous | -0.278 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| D/T | 0.7319 | likely_pathogenic | 0.6948 | pathogenic | -0.084 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| D/V | 0.8691 | likely_pathogenic | 0.8541 | pathogenic | 0.543 | Stabilizing | 1.0 | D | 0.778 | deleterious | N | 0.513390646 | None | None | N |
| D/W | 0.9945 | likely_pathogenic | 0.9937 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/Y | 0.83 | likely_pathogenic | 0.8001 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | D | 0.546752 | 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.