Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31414 | 94465;94466;94467 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| N2AB | 29773 | 89542;89543;89544 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| N2A | 28846 | 86761;86762;86763 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| N2B | 22349 | 67270;67271;67272 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| Novex-1 | 22474 | 67645;67646;67647 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| Novex-2 | 22541 | 67846;67847;67848 | chr2:178547285;178547284;178547283 | chr2:179412012;179412011;179412010 |
| 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/G | rs369418580  |
-0.334 | 1.0 | N | 0.665 | 0.365 | None | gnomAD-2.1.1 | 1.8E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 8.05E-05 | 2.36E-05 | 0 |
| R/G | rs369418580 |
-0.334 | 1.0 | N | 0.665 | 0.365 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/G | rs369418580 |
-0.334 | 1.0 | N | 0.665 | 0.365 | None | gnomAD-4.0.0 | 1.80127E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.25763E-05 | 0 | 2.12312E-05 | 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 | 0.6904 | likely_pathogenic | 0.6859 | pathogenic | -0.622 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| R/C | 0.3325 | likely_benign | 0.3301 | benign | -0.523 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/D | 0.9568 | likely_pathogenic | 0.9534 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/E | 0.8093 | likely_pathogenic | 0.7994 | pathogenic | -0.051 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| R/F | 0.8322 | likely_pathogenic | 0.8299 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/G | 0.6728 | likely_pathogenic | 0.6663 | pathogenic | -0.88 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.444962478 | None | None | N |
| R/H | 0.2549 | likely_benign | 0.2483 | benign | -1.222 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/I | 0.5955 | likely_pathogenic | 0.5877 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.749 | deleterious | N | 0.461510798 | None | None | N |
| R/K | 0.1752 | likely_benign | 0.1622 | benign | -0.681 | Destabilizing | 0.997 | D | 0.535 | neutral | N | 0.385474244 | None | None | N |
| R/L | 0.5417 | ambiguous | 0.5312 | ambiguous | 0.051 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| R/M | 0.6142 | likely_pathogenic | 0.6149 | pathogenic | -0.135 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/N | 0.8968 | likely_pathogenic | 0.8885 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/P | 0.7129 | likely_pathogenic | 0.7106 | pathogenic | -0.153 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/Q | 0.2291 | likely_benign | 0.2172 | benign | -0.347 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| R/S | 0.8158 | likely_pathogenic | 0.8093 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.441847602 | None | None | N |
| R/T | 0.625 | likely_pathogenic | 0.6079 | pathogenic | -0.534 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.436460425 | None | None | N |
| R/V | 0.6467 | likely_pathogenic | 0.6327 | pathogenic | -0.153 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/W | 0.4384 | ambiguous | 0.4333 | ambiguous | -0.45 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Y | 0.7049 | likely_pathogenic | 0.6964 | pathogenic | -0.117 | Destabilizing | 1.0 | D | 0.755 | 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.