Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25806 | 77641;77642;77643 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| N2AB | 24165 | 72718;72719;72720 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| N2A | 23238 | 69937;69938;69939 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| N2B | 16741 | 50446;50447;50448 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| Novex-1 | 16866 | 50821;50822;50823 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| Novex-2 | 16933 | 51022;51023;51024 | chr2:178568716;178568715;178568714 | chr2:179433443;179433442;179433441 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs1405741278  |
None | None | N | 0.088 | 0.085 | 0.0401082797425 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1405741278 |
None | None | N | 0.088 | 0.085 | 0.0401082797425 | gnomAD-4.0.0 | 2.47957E-06 | None | None | None | None | N | None | 2.67087E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47779E-07 | 0 | 1.60159E-05 |
| S/R | rs759686148 |
0.027 | 0.317 | N | 0.366 | 0.182 | 0.207176502487 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0985 | likely_benign | 0.0884 | benign | -0.708 | Destabilizing | 0.035 | N | 0.329 | neutral | None | None | None | None | N |
| S/C | 0.0882 | likely_benign | 0.088 | benign | -0.421 | Destabilizing | 0.915 | D | 0.36 | neutral | N | 0.470330557 | None | None | N |
| S/D | 0.4294 | ambiguous | 0.426 | ambiguous | 0.615 | Stabilizing | 0.081 | N | 0.267 | neutral | None | None | None | None | N |
| S/E | 0.5572 | ambiguous | 0.5506 | ambiguous | 0.621 | Stabilizing | 0.081 | N | 0.268 | neutral | None | None | None | None | N |
| S/F | 0.2345 | likely_benign | 0.2047 | benign | -1.009 | Destabilizing | 0.555 | D | 0.451 | neutral | None | None | None | None | N |
| S/G | 0.0881 | likely_benign | 0.0912 | benign | -0.933 | Destabilizing | 0.027 | N | 0.271 | neutral | N | 0.501423475 | None | None | N |
| S/H | 0.2157 | likely_benign | 0.2179 | benign | -1.218 | Destabilizing | 0.38 | N | 0.363 | neutral | None | None | None | None | N |
| S/I | 0.1407 | likely_benign | 0.1337 | benign | -0.217 | Destabilizing | 0.188 | N | 0.451 | neutral | N | 0.51333398 | None | None | N |
| S/K | 0.5034 | ambiguous | 0.5024 | ambiguous | -0.194 | Destabilizing | 0.081 | N | 0.257 | neutral | None | None | None | None | N |
| S/L | 0.1213 | likely_benign | 0.1092 | benign | -0.217 | Destabilizing | 0.081 | N | 0.396 | neutral | None | None | None | None | N |
| S/M | 0.1956 | likely_benign | 0.1718 | benign | -0.195 | Destabilizing | 0.555 | D | 0.358 | neutral | None | None | None | None | N |
| S/N | 0.0881 | likely_benign | 0.0865 | benign | -0.181 | Destabilizing | None | N | 0.088 | neutral | N | 0.448242352 | None | None | N |
| S/P | 0.5815 | likely_pathogenic | 0.6014 | pathogenic | -0.349 | Destabilizing | 0.555 | D | 0.363 | neutral | None | None | None | None | N |
| S/Q | 0.385 | ambiguous | 0.3817 | ambiguous | -0.239 | Destabilizing | 0.38 | N | 0.351 | neutral | None | None | None | None | N |
| S/R | 0.4322 | ambiguous | 0.4447 | ambiguous | -0.18 | Destabilizing | 0.317 | N | 0.366 | neutral | N | 0.469620488 | None | None | N |
| S/T | 0.0664 | likely_benign | 0.0615 | benign | -0.292 | Destabilizing | None | N | 0.084 | neutral | N | 0.380577352 | None | None | N |
| S/V | 0.1506 | likely_benign | 0.1357 | benign | -0.349 | Destabilizing | 0.081 | N | 0.396 | neutral | None | None | None | None | N |
| S/W | 0.4115 | ambiguous | 0.3975 | ambiguous | -0.97 | Destabilizing | 0.935 | D | 0.539 | neutral | None | None | None | None | N |
| S/Y | 0.1813 | likely_benign | 0.1756 | benign | -0.669 | Destabilizing | 0.555 | D | 0.451 | 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.