Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22440 | 67543;67544;67545 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| N2AB | 20799 | 62620;62621;62622 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| N2A | 19872 | 59839;59840;59841 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| N2B | 13375 | 40348;40349;40350 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| Novex-1 | 13500 | 40723;40724;40725 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| Novex-2 | 13567 | 40924;40925;40926 | chr2:178579969;178579968;178579967 | chr2:179444696;179444695;179444694 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | rs2047328766  |
None | 0.309 | N | 0.56 | 0.154 | 0.19670166235 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| G/A | rs2047328766 |
None | 0.309 | N | 0.56 | 0.154 | 0.19670166235 | gnomAD-4.0.0 | 6.57644E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47089E-05 | 0 | 0 |
| G/C | rs727503576 |
-0.348 | 0.007 | N | 0.544 | 0.226 | 0.220303561663 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| G/C | rs727503576 |
-0.348 | 0.007 | N | 0.544 | 0.226 | 0.220303561663 | gnomAD-4.0.0 | 3.42245E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.79979E-05 | 0 |
| G/S | rs727503576 |
None | 0.924 | N | 0.619 | 0.089 | 0.144782658237 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| G/S | rs727503576 |
None | 0.924 | N | 0.619 | 0.089 | 0.144782658237 | gnomAD-4.0.0 | 9.29982E-06 | None | None | None | None | I | None | 2.67201E-05 | 3.33622E-05 | None | 0 | 0 | None | 0 | 0 | 9.32624E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.086 | likely_benign | 0.094 | benign | -0.666 | Destabilizing | 0.309 | N | 0.56 | neutral | N | 0.440380591 | None | None | I |
| G/C | 0.1393 | likely_benign | 0.1507 | benign | -0.738 | Destabilizing | 0.007 | N | 0.544 | neutral | N | 0.494119075 | None | None | I |
| G/D | 0.6608 | likely_pathogenic | 0.7257 | pathogenic | -1.959 | Destabilizing | 0.979 | D | 0.563 | neutral | N | 0.483075362 | None | None | I |
| G/E | 0.4521 | ambiguous | 0.5179 | ambiguous | -1.827 | Destabilizing | 0.953 | D | 0.593 | neutral | None | None | None | None | I |
| G/F | 0.664 | likely_pathogenic | 0.6959 | pathogenic | -0.579 | Destabilizing | 0.835 | D | 0.631 | neutral | None | None | None | None | I |
| G/H | 0.6868 | likely_pathogenic | 0.7305 | pathogenic | -1.782 | Destabilizing | 0.974 | D | 0.559 | neutral | None | None | None | None | I |
| G/I | 0.2878 | likely_benign | 0.3396 | benign | 0.272 | Stabilizing | 0.59 | D | 0.647 | neutral | None | None | None | None | I |
| G/K | 0.6655 | likely_pathogenic | 0.7317 | pathogenic | -1.131 | Destabilizing | 0.953 | D | 0.591 | neutral | None | None | None | None | I |
| G/L | 0.5118 | ambiguous | 0.5716 | pathogenic | 0.272 | Stabilizing | 0.59 | D | 0.648 | neutral | None | None | None | None | I |
| G/M | 0.4991 | ambiguous | 0.5532 | ambiguous | 0.078 | Stabilizing | 0.987 | D | 0.611 | neutral | None | None | None | None | I |
| G/N | 0.617 | likely_pathogenic | 0.6687 | pathogenic | -1.202 | Destabilizing | 0.953 | D | 0.615 | neutral | None | None | None | None | I |
| G/P | 0.9856 | likely_pathogenic | 0.9885 | pathogenic | 0.002 | Stabilizing | 0.984 | D | 0.581 | neutral | None | None | None | None | I |
| G/Q | 0.4989 | ambiguous | 0.5575 | ambiguous | -1.095 | Destabilizing | 0.953 | D | 0.571 | neutral | None | None | None | None | I |
| G/R | 0.4725 | ambiguous | 0.5384 | ambiguous | -1.184 | Destabilizing | 0.975 | D | 0.587 | neutral | N | 0.512531477 | None | None | I |
| G/S | 0.1331 | likely_benign | 0.1504 | benign | -1.48 | Destabilizing | 0.924 | D | 0.619 | neutral | N | 0.353942537 | None | None | I |
| G/T | 0.1795 | likely_benign | 0.2138 | benign | -1.256 | Destabilizing | 0.742 | D | 0.614 | neutral | None | None | None | None | I |
| G/V | 0.1669 | likely_benign | 0.2018 | benign | 0.002 | Stabilizing | 0.028 | N | 0.635 | neutral | N | 0.493252283 | None | None | I |
| G/W | 0.6388 | likely_pathogenic | 0.6885 | pathogenic | -1.389 | Destabilizing | 0.987 | D | 0.571 | neutral | None | None | None | None | I |
| G/Y | 0.6113 | likely_pathogenic | 0.6587 | pathogenic | -0.78 | Destabilizing | 0.02 | N | 0.615 | 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.