Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18778 | 56557;56558;56559 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| N2AB | 17137 | 51634;51635;51636 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| N2A | 16210 | 48853;48854;48855 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| N2B | 9713 | 29362;29363;29364 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| Novex-1 | 9838 | 29737;29738;29739 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| Novex-2 | 9905 | 29938;29939;29940 | chr2:178599569;178599568;178599567 | chr2:179464296;179464295;179464294 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs1178812946  |
None | 0.998 | N | 0.679 | 0.418 | 0.696300106271 | gnomAD-4.0.0 | 1.4046E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.53145E-05 | 0 |
| R/K | None | None | 0.122 | N | 0.182 | 0.111 | 0.19670166235 | gnomAD-4.0.0 | 7.02302E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.15127E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7777 | likely_pathogenic | 0.7225 | pathogenic | -0.987 | Destabilizing | 0.931 | D | 0.569 | neutral | None | None | None | None | N |
| R/C | 0.3189 | likely_benign | 0.2956 | benign | -0.916 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/D | 0.9149 | likely_pathogenic | 0.8836 | pathogenic | -0.058 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.6777 | likely_pathogenic | 0.6266 | pathogenic | 0.125 | Stabilizing | 0.97 | D | 0.544 | neutral | None | None | None | None | N |
| R/F | 0.7256 | likely_pathogenic | 0.6867 | pathogenic | -0.435 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/G | 0.7372 | likely_pathogenic | 0.6653 | pathogenic | -1.353 | Destabilizing | 0.98 | D | 0.613 | neutral | N | 0.491390776 | None | None | N |
| R/H | 0.1716 | likely_benign | 0.153 | benign | -1.463 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/I | 0.4134 | ambiguous | 0.3775 | ambiguous | 0.028 | Stabilizing | 0.998 | D | 0.679 | prob.neutral | N | 0.510644044 | None | None | N |
| R/K | 0.1975 | likely_benign | 0.1787 | benign | -0.766 | Destabilizing | 0.122 | N | 0.182 | neutral | N | 0.443013543 | None | None | N |
| R/L | 0.4029 | ambiguous | 0.3665 | ambiguous | 0.028 | Stabilizing | 0.985 | D | 0.613 | neutral | None | None | None | None | N |
| R/M | 0.4755 | ambiguous | 0.4273 | ambiguous | -0.483 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| R/N | 0.8312 | likely_pathogenic | 0.7753 | pathogenic | -0.483 | Destabilizing | 0.985 | D | 0.577 | neutral | None | None | None | None | N |
| R/P | 0.9178 | likely_pathogenic | 0.8946 | pathogenic | -0.291 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| R/Q | 0.1996 | likely_benign | 0.1803 | benign | -0.487 | Destabilizing | 0.97 | D | 0.594 | neutral | None | None | None | None | N |
| R/S | 0.8299 | likely_pathogenic | 0.7799 | pathogenic | -1.301 | Destabilizing | 0.961 | D | 0.598 | neutral | N | 0.483262655 | None | None | N |
| R/T | 0.5438 | ambiguous | 0.4722 | ambiguous | -0.904 | Destabilizing | 0.98 | D | 0.621 | neutral | N | 0.477856835 | None | None | N |
| R/V | 0.5452 | ambiguous | 0.5101 | ambiguous | -0.291 | Destabilizing | 0.996 | D | 0.643 | neutral | None | None | None | None | N |
| R/W | 0.2956 | likely_benign | 0.2653 | benign | -0.012 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| R/Y | 0.5364 | ambiguous | 0.4937 | ambiguous | 0.201 | Stabilizing | 0.999 | D | 0.682 | prob.neutral | 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.