Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3174 | 9745;9746;9747 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| N2AB | 3174 | 9745;9746;9747 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| N2A | 3174 | 9745;9746;9747 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| N2B | 3128 | 9607;9608;9609 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| Novex-1 | 3128 | 9607;9608;9609 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| Novex-2 | 3128 | 9607;9608;9609 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
| Novex-3 | 3174 | 9745;9746;9747 | chr2:178766564;178766563;178766562 | chr2:179631291;179631290;179631289 |
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 | 0.999 | D | 0.655 | 0.559 | 0.578554888259 | gnomAD-4.0.0 | 1.59067E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85659E-06 | 0 | 0 |
| D/N | rs984157404  |
0.647 | 1.0 | N | 0.715 | 0.368 | 0.347879110917 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | I | None | 4E-05 | 2.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.77E-06 | 0 |
| D/N | rs984157404 |
0.647 | 1.0 | N | 0.715 | 0.368 | 0.347879110917 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs984157404 |
0.647 | 1.0 | N | 0.715 | 0.368 | 0.347879110917 | gnomAD-4.0.0 | 5.57641E-06 | None | None | None | None | I | None | 4.00384E-05 | 1.667E-05 | None | 0 | 4.45831E-05 | None | 0 | 0 | 2.54239E-06 | 0 | 0 |
| D/Y | None | None | 1.0 | D | 0.673 | 0.631 | 0.781116581806 | gnomAD-4.0.0 | 6.84103E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99311E-07 | 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 | 0.5723 | likely_pathogenic | 0.545 | ambiguous | 0.116 | Stabilizing | 0.999 | D | 0.655 | neutral | D | 0.52995995 | None | None | I |
| D/C | 0.9603 | likely_pathogenic | 0.9579 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/E | 0.3971 | ambiguous | 0.3665 | ambiguous | -0.314 | Destabilizing | 0.767 | D | 0.367 | neutral | N | 0.499865701 | None | None | I |
| D/F | 0.8876 | likely_pathogenic | 0.8868 | pathogenic | -0.064 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| D/G | 0.5016 | ambiguous | 0.4732 | ambiguous | 0.029 | Stabilizing | 0.998 | D | 0.689 | prob.neutral | D | 0.549617585 | None | None | I |
| D/H | 0.7859 | likely_pathogenic | 0.7571 | pathogenic | 0.536 | Stabilizing | 1.0 | D | 0.663 | neutral | D | 0.615900385 | None | None | I |
| D/I | 0.8431 | likely_pathogenic | 0.8371 | pathogenic | 0.272 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/K | 0.8558 | likely_pathogenic | 0.8466 | pathogenic | 0.462 | Stabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/L | 0.8079 | likely_pathogenic | 0.7988 | pathogenic | 0.272 | Stabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| D/M | 0.9178 | likely_pathogenic | 0.91 | pathogenic | 0.067 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/N | 0.2624 | likely_benign | 0.2476 | benign | 0.338 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.51419796 | None | None | I |
| D/P | 0.9796 | likely_pathogenic | 0.9692 | pathogenic | 0.238 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/Q | 0.8331 | likely_pathogenic | 0.8107 | pathogenic | 0.314 | Stabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | None | I |
| D/R | 0.8565 | likely_pathogenic | 0.8417 | pathogenic | 0.641 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| D/S | 0.4171 | ambiguous | 0.3855 | ambiguous | 0.223 | Stabilizing | 0.997 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/T | 0.6663 | likely_pathogenic | 0.6406 | pathogenic | 0.295 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/V | 0.6943 | likely_pathogenic | 0.6856 | pathogenic | 0.238 | Stabilizing | 0.999 | D | 0.675 | neutral | D | 0.548613098 | None | None | I |
| D/W | 0.9846 | likely_pathogenic | 0.9818 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| D/Y | 0.6612 | likely_pathogenic | 0.6494 | pathogenic | 0.155 | Stabilizing | 1.0 | D | 0.673 | neutral | D | 0.617323052 | 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.