Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24471 | 73636;73637;73638 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| N2AB | 22830 | 68713;68714;68715 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| N2A | 21903 | 65932;65933;65934 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| N2B | 15406 | 46441;46442;46443 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| Novex-1 | 15531 | 46816;46817;46818 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| Novex-2 | 15598 | 47017;47018;47019 | chr2:178572721;178572720;178572719 | chr2:179437448;179437447;179437446 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1471781546  |
-0.189 | 0.892 | N | 0.478 | 0.155 | 0.195762928549 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs1471781546 |
-0.189 | 0.892 | N | 0.478 | 0.155 | 0.195762928549 | gnomAD-4.0.0 | 3.18374E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.8659E-05 | 0 |
| D/H | rs1708675722 |
None | 0.995 | N | 0.481 | 0.324 | 0.284150004643 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.1394 | likely_benign | 0.1477 | benign | 0.092 | Stabilizing | 0.805 | D | 0.505 | neutral | N | 0.503770347 | None | None | N |
| D/C | 0.4808 | ambiguous | 0.5068 | ambiguous | -0.067 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| D/E | 0.0806 | likely_benign | 0.0858 | benign | -0.304 | Destabilizing | 0.025 | N | 0.355 | neutral | N | 0.407473164 | None | None | N |
| D/F | 0.5267 | ambiguous | 0.5723 | pathogenic | -0.027 | Destabilizing | 0.975 | D | 0.611 | neutral | None | None | None | None | N |
| D/G | 0.1191 | likely_benign | 0.1205 | benign | -0.002 | Destabilizing | 0.892 | D | 0.478 | neutral | N | 0.479237262 | None | None | N |
| D/H | 0.2299 | likely_benign | 0.2346 | benign | 0.54 | Stabilizing | 0.995 | D | 0.481 | neutral | N | 0.470215198 | None | None | N |
| D/I | 0.2935 | likely_benign | 0.3234 | benign | 0.27 | Stabilizing | 0.95 | D | 0.575 | neutral | None | None | None | None | N |
| D/K | 0.2714 | likely_benign | 0.2864 | benign | 0.503 | Stabilizing | 0.845 | D | 0.471 | neutral | None | None | None | None | N |
| D/L | 0.2738 | likely_benign | 0.2955 | benign | 0.27 | Stabilizing | 0.95 | D | 0.511 | neutral | None | None | None | None | N |
| D/M | 0.4491 | ambiguous | 0.5033 | ambiguous | 0.09 | Stabilizing | 0.997 | D | 0.614 | neutral | None | None | None | None | N |
| D/N | 0.107 | likely_benign | 0.1117 | benign | 0.254 | Stabilizing | 0.967 | D | 0.449 | neutral | N | 0.465252032 | None | None | N |
| D/P | 0.3818 | ambiguous | 0.3963 | ambiguous | 0.229 | Stabilizing | 0.987 | D | 0.485 | neutral | None | None | None | None | N |
| D/Q | 0.1964 | likely_benign | 0.2083 | benign | 0.264 | Stabilizing | 0.95 | D | 0.483 | neutral | None | None | None | None | N |
| D/R | 0.3121 | likely_benign | 0.337 | benign | 0.655 | Stabilizing | 0.975 | D | 0.567 | neutral | None | None | None | None | N |
| D/S | 0.1053 | likely_benign | 0.1098 | benign | 0.188 | Stabilizing | 0.916 | D | 0.48 | neutral | None | None | None | None | N |
| D/T | 0.1741 | likely_benign | 0.1897 | benign | 0.273 | Stabilizing | 0.975 | D | 0.448 | neutral | None | None | None | None | N |
| D/V | 0.177 | likely_benign | 0.188 | benign | 0.229 | Stabilizing | 0.056 | N | 0.479 | neutral | N | 0.465949237 | None | None | N |
| D/W | 0.79 | likely_pathogenic | 0.8116 | pathogenic | -0.015 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2559 | likely_benign | 0.2715 | benign | 0.188 | Stabilizing | 0.983 | D | 0.61 | neutral | N | 0.476798563 | 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.