Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20575 | 61948;61949;61950 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| N2AB | 18934 | 57025;57026;57027 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| N2A | 18007 | 54244;54245;54246 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| N2B | 11510 | 34753;34754;34755 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| Novex-1 | 11635 | 35128;35129;35130 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| Novex-2 | 11702 | 35329;35330;35331 | chr2:178590002;178590001;178590000 | chr2:179454729;179454728;179454727 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs779775208  |
0.385 | 0.977 | N | 0.511 | 0.338 | 0.258779203287 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| N/D | rs779775208 |
0.385 | 0.977 | N | 0.511 | 0.338 | 0.258779203287 | gnomAD-4.0.0 | 1.3689E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79932E-06 | 0 | 0 |
| N/H | rs779775208 |
-0.429 | 0.235 | N | 0.263 | 0.306 | 0.235038932564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| N/H | rs779775208 |
-0.429 | 0.235 | N | 0.263 | 0.306 | 0.235038932564 | gnomAD-4.0.0 | 2.05336E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69898E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4244 | ambiguous | 0.3895 | ambiguous | -0.339 | Destabilizing | 0.983 | D | 0.583 | neutral | None | None | None | None | N |
| N/C | 0.4934 | ambiguous | 0.4787 | ambiguous | 0.265 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| N/D | 0.2232 | likely_benign | 0.2137 | benign | 0.083 | Stabilizing | 0.977 | D | 0.511 | neutral | N | 0.473405447 | None | None | N |
| N/E | 0.5648 | likely_pathogenic | 0.5168 | ambiguous | 0.075 | Stabilizing | 0.983 | D | 0.555 | neutral | None | None | None | None | N |
| N/F | 0.6656 | likely_pathogenic | 0.6426 | pathogenic | -0.549 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| N/G | 0.4053 | ambiguous | 0.4039 | ambiguous | -0.554 | Destabilizing | 0.983 | D | 0.466 | neutral | None | None | None | None | N |
| N/H | 0.1838 | likely_benign | 0.1692 | benign | -0.51 | Destabilizing | 0.235 | N | 0.263 | neutral | N | 0.493305517 | None | None | N |
| N/I | 0.4598 | ambiguous | 0.405 | ambiguous | 0.148 | Stabilizing | 0.997 | D | 0.735 | prob.delet. | N | 0.495925636 | None | None | N |
| N/K | 0.4341 | ambiguous | 0.3687 | ambiguous | -0.027 | Destabilizing | 0.977 | D | 0.58 | neutral | N | 0.502536275 | None | None | N |
| N/L | 0.4373 | ambiguous | 0.3939 | ambiguous | 0.148 | Stabilizing | 0.995 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/M | 0.5031 | ambiguous | 0.4718 | ambiguous | 0.371 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| N/P | 0.9134 | likely_pathogenic | 0.916 | pathogenic | 0.014 | Stabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| N/Q | 0.4459 | ambiguous | 0.407 | ambiguous | -0.46 | Destabilizing | 0.995 | D | 0.648 | neutral | None | None | None | None | N |
| N/R | 0.5375 | ambiguous | 0.4804 | ambiguous | 0.001 | Stabilizing | 0.995 | D | 0.614 | neutral | None | None | None | None | N |
| N/S | 0.1771 | likely_benign | 0.1643 | benign | -0.293 | Destabilizing | 0.977 | D | 0.469 | neutral | N | 0.521295394 | None | None | N |
| N/T | 0.2889 | likely_benign | 0.2632 | benign | -0.148 | Destabilizing | 0.989 | D | 0.583 | neutral | N | 0.484404747 | None | None | N |
| N/V | 0.4709 | ambiguous | 0.4226 | ambiguous | 0.014 | Stabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| N/W | 0.9115 | likely_pathogenic | 0.8932 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/Y | 0.257 | likely_benign | 0.2392 | benign | -0.257 | Destabilizing | 0.993 | D | 0.705 | prob.neutral | D | 0.523019567 | 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.