Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15984 | 48175;48176;48177 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| N2AB | 14343 | 43252;43253;43254 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| N2A | 13416 | 40471;40472;40473 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| N2B | 6919 | 20980;20981;20982 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| Novex-1 | 7044 | 21355;21356;21357 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| Novex-2 | 7111 | 21556;21557;21558 | chr2:178616939;178616938;178616937 | chr2:179481666;179481665;179481664 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs766367585  |
0.308 | 0.997 | D | 0.698 | 0.335 | 0.534046140783 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63409E-04 | None | 0 | 0 | 0 |
| V/L | rs766367585 |
0.308 | 0.997 | D | 0.698 | 0.335 | 0.534046140783 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 4.79386E-04 |
| V/L | rs766367585 |
0.308 | 0.997 | D | 0.698 | 0.335 | 0.534046140783 | gnomAD-4.0.0 | 1.15473E-05 | None | None | None | None | N | None | 0 | 1.69745E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 9.38313E-05 | 2.84965E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7968 | likely_pathogenic | 0.8139 | pathogenic | -1.453 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | N | 0.483830711 | None | None | N |
| V/C | 0.9436 | likely_pathogenic | 0.9427 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| V/D | 0.9949 | likely_pathogenic | 0.9957 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.911 | deleterious | D | 0.608121527 | None | None | N |
| V/E | 0.9839 | likely_pathogenic | 0.987 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| V/F | 0.7478 | likely_pathogenic | 0.7669 | pathogenic | -0.869 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.607972652 | None | None | N |
| V/G | 0.9057 | likely_pathogenic | 0.9184 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.906 | deleterious | D | 0.568518109 | None | None | N |
| V/H | 0.9924 | likely_pathogenic | 0.993 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.926 | deleterious | None | None | None | None | N |
| V/I | 0.1139 | likely_benign | 0.1145 | benign | -0.174 | Destabilizing | 0.997 | D | 0.589 | neutral | N | 0.443482176 | None | None | N |
| V/K | 0.9841 | likely_pathogenic | 0.9861 | pathogenic | -0.994 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| V/L | 0.5479 | ambiguous | 0.5865 | pathogenic | -0.174 | Destabilizing | 0.997 | D | 0.698 | prob.neutral | D | 0.563595358 | None | None | N |
| V/M | 0.731 | likely_pathogenic | 0.7557 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| V/N | 0.9848 | likely_pathogenic | 0.9864 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.935 | deleterious | None | None | None | None | N |
| V/P | 0.9792 | likely_pathogenic | 0.9787 | pathogenic | -0.573 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| V/Q | 0.9749 | likely_pathogenic | 0.9784 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.937 | deleterious | None | None | None | None | N |
| V/R | 0.9663 | likely_pathogenic | 0.9707 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.938 | deleterious | None | None | None | None | N |
| V/S | 0.9353 | likely_pathogenic | 0.9407 | pathogenic | -1.942 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| V/T | 0.9007 | likely_pathogenic | 0.9015 | pathogenic | -1.585 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| V/W | 0.9949 | likely_pathogenic | 0.9956 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| V/Y | 0.9735 | likely_pathogenic | 0.9765 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.863 | 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.