Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28660 | 86203;86204;86205 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| N2AB | 27019 | 81280;81281;81282 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| N2A | 26092 | 78499;78500;78501 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| N2B | 19595 | 59008;59009;59010 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| Novex-1 | 19720 | 59383;59384;59385 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| Novex-2 | 19787 | 59584;59585;59586 | chr2:178560154;178560153;178560152 | chr2:179424881;179424880;179424879 |
| 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 | rs397517733  |
-1.303 | 0.201 | N | 0.647 | 0.441 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 1.78E-05 | 0 |
| I/T | rs397517733 |
-1.303 | 0.201 | N | 0.647 | 0.441 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs397517733 |
-1.303 | 0.201 | N | 0.647 | 0.441 | None | gnomAD-4.0.0 | 2.91305E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.56031E-05 | 5.49076E-05 | 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 | 0.4225 | ambiguous | 0.3571 | ambiguous | -2.029 | Highly Destabilizing | 0.25 | N | 0.565 | neutral | None | None | None | None | N |
| I/C | 0.7792 | likely_pathogenic | 0.7001 | pathogenic | -1.229 | Destabilizing | 0.947 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/D | 0.9492 | likely_pathogenic | 0.9376 | pathogenic | -1.447 | Destabilizing | 0.826 | D | 0.779 | deleterious | None | None | None | None | N |
| I/E | 0.9007 | likely_pathogenic | 0.8859 | pathogenic | -1.35 | Destabilizing | 0.826 | D | 0.773 | deleterious | None | None | None | None | N |
| I/F | 0.3373 | likely_benign | 0.2227 | benign | -1.223 | Destabilizing | 0.638 | D | 0.622 | neutral | N | 0.476924965 | None | None | N |
| I/G | 0.882 | likely_pathogenic | 0.8366 | pathogenic | -2.466 | Highly Destabilizing | 0.826 | D | 0.762 | deleterious | None | None | None | None | N |
| I/H | 0.8769 | likely_pathogenic | 0.8323 | pathogenic | -1.699 | Destabilizing | 0.982 | D | 0.763 | deleterious | None | None | None | None | N |
| I/K | 0.828 | likely_pathogenic | 0.807 | pathogenic | -1.348 | Destabilizing | 0.826 | D | 0.771 | deleterious | None | None | None | None | N |
| I/L | 0.1954 | likely_benign | 0.1661 | benign | -0.844 | Destabilizing | 0.043 | N | 0.338 | neutral | N | 0.485579736 | None | None | N |
| I/M | 0.1643 | likely_benign | 0.1394 | benign | -0.685 | Destabilizing | 0.638 | D | 0.628 | neutral | N | 0.485829416 | None | None | N |
| I/N | 0.6738 | likely_pathogenic | 0.622 | pathogenic | -1.279 | Destabilizing | 0.916 | D | 0.786 | deleterious | N | 0.498110774 | None | None | N |
| I/P | 0.7575 | likely_pathogenic | 0.7295 | pathogenic | -1.211 | Destabilizing | 0.935 | D | 0.781 | deleterious | None | None | None | None | N |
| I/Q | 0.8436 | likely_pathogenic | 0.8067 | pathogenic | -1.331 | Destabilizing | 0.935 | D | 0.782 | deleterious | None | None | None | None | N |
| I/R | 0.7516 | likely_pathogenic | 0.7127 | pathogenic | -0.902 | Destabilizing | 0.826 | D | 0.787 | deleterious | None | None | None | None | N |
| I/S | 0.6117 | likely_pathogenic | 0.5302 | ambiguous | -2.018 | Highly Destabilizing | 0.638 | D | 0.72 | prob.delet. | N | 0.470687676 | None | None | N |
| I/T | 0.2901 | likely_benign | 0.2463 | benign | -1.788 | Destabilizing | 0.201 | N | 0.647 | neutral | N | 0.502376735 | None | None | N |
| I/V | 0.0723 | likely_benign | 0.0729 | benign | -1.211 | Destabilizing | 0.001 | N | 0.188 | neutral | N | 0.459121067 | None | None | N |
| I/W | 0.9141 | likely_pathogenic | 0.8776 | pathogenic | -1.389 | Destabilizing | 0.982 | D | 0.708 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7591 | likely_pathogenic | 0.6428 | pathogenic | -1.146 | Destabilizing | 0.826 | D | 0.736 | prob.delet. | 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.