Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2766 | 8521;8522;8523 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| N2AB | 2766 | 8521;8522;8523 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| N2A | 2766 | 8521;8522;8523 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| N2B | 2720 | 8383;8384;8385 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| Novex-1 | 2720 | 8383;8384;8385 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| Novex-2 | 2720 | 8383;8384;8385 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
| Novex-3 | 2766 | 8521;8522;8523 | chr2:178770496;178770495;178770494 | chr2:179635223;179635222;179635221 |
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/F | rs1414224093  |
-1.739 | 0.901 | D | 0.727 | 0.685 | 0.594255065555 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs1414224093 |
-1.739 | 0.901 | D | 0.727 | 0.685 | 0.594255065555 | gnomAD-4.0.0 | 1.5905E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77346E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs755389555 |
-3.105 | 0.722 | D | 0.711 | 0.648 | 0.817529497908 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/T | rs755389555 |
-3.105 | 0.722 | D | 0.711 | 0.648 | 0.817529497908 | gnomAD-4.0.0 | 1.59051E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85651E-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 | 0.9393 | likely_pathogenic | 0.952 | pathogenic | -3.09 | Highly Destabilizing | 0.415 | N | 0.701 | prob.neutral | None | None | None | None | N |
| I/C | 0.9403 | likely_pathogenic | 0.9527 | pathogenic | -2.446 | Highly Destabilizing | 0.996 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9969 | likely_pathogenic | 0.9976 | pathogenic | -3.799 | Highly Destabilizing | 0.858 | D | 0.827 | deleterious | None | None | None | None | N |
| I/E | 0.9856 | likely_pathogenic | 0.9895 | pathogenic | -3.507 | Highly Destabilizing | 0.923 | D | 0.825 | deleterious | None | None | None | None | N |
| I/F | 0.6238 | likely_pathogenic | 0.6915 | pathogenic | -1.826 | Destabilizing | 0.901 | D | 0.727 | prob.delet. | D | 0.606500169 | None | None | N |
| I/G | 0.9861 | likely_pathogenic | 0.989 | pathogenic | -3.669 | Highly Destabilizing | 0.633 | D | 0.827 | deleterious | None | None | None | None | N |
| I/H | 0.9815 | likely_pathogenic | 0.9867 | pathogenic | -3.261 | Highly Destabilizing | 0.989 | D | 0.845 | deleterious | None | None | None | None | N |
| I/K | 0.969 | likely_pathogenic | 0.9777 | pathogenic | -2.467 | Highly Destabilizing | 0.923 | D | 0.828 | deleterious | None | None | None | None | N |
| I/L | 0.2383 | likely_benign | 0.2891 | benign | -1.348 | Destabilizing | 0.349 | N | 0.465 | neutral | D | 0.543018071 | None | None | N |
| I/M | 0.2543 | likely_benign | 0.2916 | benign | -1.491 | Destabilizing | 0.901 | D | 0.687 | prob.neutral | D | 0.670443272 | None | None | N |
| I/N | 0.9494 | likely_pathogenic | 0.9568 | pathogenic | -3.089 | Highly Destabilizing | 0.018 | N | 0.644 | neutral | D | 0.705038183 | None | None | N |
| I/P | 0.9941 | likely_pathogenic | 0.9957 | pathogenic | -1.92 | Destabilizing | 0.987 | D | 0.856 | deleterious | None | None | None | None | N |
| I/Q | 0.9675 | likely_pathogenic | 0.9768 | pathogenic | -2.8 | Highly Destabilizing | 0.961 | D | 0.851 | deleterious | None | None | None | None | N |
| I/R | 0.9572 | likely_pathogenic | 0.9686 | pathogenic | -2.303 | Highly Destabilizing | 0.923 | D | 0.855 | deleterious | None | None | None | None | N |
| I/S | 0.9585 | likely_pathogenic | 0.9645 | pathogenic | -3.675 | Highly Destabilizing | 0.565 | D | 0.805 | deleterious | D | 0.705038183 | None | None | N |
| I/T | 0.9538 | likely_pathogenic | 0.9605 | pathogenic | -3.236 | Highly Destabilizing | 0.722 | D | 0.711 | prob.delet. | D | 0.705208095 | None | None | N |
| I/V | 0.1062 | likely_benign | 0.1155 | benign | -1.92 | Destabilizing | 0.003 | N | 0.243 | neutral | D | 0.541592401 | None | None | N |
| I/W | 0.9847 | likely_pathogenic | 0.9894 | pathogenic | -2.315 | Highly Destabilizing | 0.996 | D | 0.829 | deleterious | None | None | None | None | N |
| I/Y | 0.9395 | likely_pathogenic | 0.954 | pathogenic | -2.147 | Highly Destabilizing | 0.961 | D | 0.767 | deleterious | 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.