Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32846 | 98761;98762;98763 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| N2AB | 31205 | 93838;93839;93840 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| N2A | 30278 | 91057;91058;91059 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| N2B | 23781 | 71566;71567;71568 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| Novex-1 | 23906 | 71941;71942;71943 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| Novex-2 | 23973 | 72142;72143;72144 | chr2:178539529;178539528;178539527 | chr2:179404256;179404255;179404254 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs762000616  |
-1.755 | 0.549 | N | 0.519 | 0.329 | 0.507928266286 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 8.48E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs762000616 |
-1.755 | 0.549 | N | 0.519 | 0.329 | 0.507928266286 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs762000616 |
-1.755 | 0.549 | N | 0.519 | 0.329 | 0.507928266286 | gnomAD-4.0.0 | 5.1246E-06 | None | None | None | None | I | None | 1.69268E-05 | 3.38995E-05 | None | 0 | 0 | None | 0 | 0 | 2.39301E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3736 | ambiguous | 0.2875 | benign | -1.689 | Destabilizing | 0.25 | N | 0.432 | neutral | None | None | None | None | I |
| I/C | 0.8223 | likely_pathogenic | 0.775 | pathogenic | -1.184 | Destabilizing | 0.992 | D | 0.553 | neutral | None | None | None | None | I |
| I/D | 0.9652 | likely_pathogenic | 0.941 | pathogenic | -0.933 | Destabilizing | 0.972 | D | 0.602 | neutral | None | None | None | None | I |
| I/E | 0.9041 | likely_pathogenic | 0.8514 | pathogenic | -0.863 | Destabilizing | 0.92 | D | 0.597 | neutral | None | None | None | None | I |
| I/F | 0.609 | likely_pathogenic | 0.5248 | ambiguous | -1.029 | Destabilizing | 0.81 | D | 0.504 | neutral | N | 0.488723537 | None | None | I |
| I/G | 0.8895 | likely_pathogenic | 0.8176 | pathogenic | -2.074 | Highly Destabilizing | 0.766 | D | 0.558 | neutral | None | None | None | None | I |
| I/H | 0.9366 | likely_pathogenic | 0.899 | pathogenic | -1.2 | Destabilizing | 0.992 | D | 0.605 | neutral | None | None | None | None | I |
| I/K | 0.9015 | likely_pathogenic | 0.8456 | pathogenic | -1.151 | Destabilizing | 0.92 | D | 0.597 | neutral | None | None | None | None | I |
| I/L | 0.2326 | likely_benign | 0.1998 | benign | -0.679 | Destabilizing | 0.045 | N | 0.307 | neutral | N | 0.425498778 | None | None | I |
| I/M | 0.1782 | likely_benign | 0.1584 | benign | -0.654 | Destabilizing | 0.81 | D | 0.549 | neutral | N | 0.4782959 | None | None | I |
| I/N | 0.7813 | likely_pathogenic | 0.6873 | pathogenic | -1.151 | Destabilizing | 0.963 | D | 0.609 | neutral | N | 0.461933085 | None | None | I |
| I/P | 0.9444 | likely_pathogenic | 0.9173 | pathogenic | -0.985 | Destabilizing | 0.972 | D | 0.611 | neutral | None | None | None | None | I |
| I/Q | 0.872 | likely_pathogenic | 0.8118 | pathogenic | -1.2 | Destabilizing | 0.972 | D | 0.621 | neutral | None | None | None | None | I |
| I/R | 0.8546 | likely_pathogenic | 0.775 | pathogenic | -0.68 | Destabilizing | 0.92 | D | 0.611 | neutral | None | None | None | None | I |
| I/S | 0.5583 | ambiguous | 0.4502 | ambiguous | -1.849 | Destabilizing | 0.549 | D | 0.542 | neutral | N | 0.502634197 | None | None | I |
| I/T | 0.2288 | likely_benign | 0.1753 | benign | -1.64 | Destabilizing | 0.549 | D | 0.519 | neutral | N | 0.498593814 | None | None | I |
| I/V | 0.067 | likely_benign | 0.0618 | benign | -0.985 | Destabilizing | 0.001 | N | 0.147 | neutral | N | 0.32708401 | None | None | I |
| I/W | 0.9692 | likely_pathogenic | 0.9542 | pathogenic | -1.133 | Destabilizing | 0.992 | D | 0.631 | neutral | None | None | None | None | I |
| I/Y | 0.9192 | likely_pathogenic | 0.8784 | pathogenic | -0.882 | Destabilizing | 0.92 | D | 0.571 | neutral | None | None | None | None | I |
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.