Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1713 | 5362;5363;5364 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| N2AB | 1713 | 5362;5363;5364 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| N2A | 1713 | 5362;5363;5364 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| N2B | 1667 | 5224;5225;5226 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| Novex-1 | 1667 | 5224;5225;5226 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| Novex-2 | 1667 | 5224;5225;5226 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
| Novex-3 | 1713 | 5362;5363;5364 | chr2:178776727;178776726;178776725 | chr2:179641454;179641453;179641452 |
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/K | rs890589931  |
None | 0.997 | N | 0.569 | 0.375 | 0.311387274539 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs890589931 |
None | 0.997 | N | 0.569 | 0.375 | 0.311387274539 | gnomAD-4.0.0 | 1.92076E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54233E-05 | 0 | 1.60046E-05 |
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 | 0.8627 | likely_pathogenic | 0.8377 | pathogenic | -0.255 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| R/C | 0.5428 | ambiguous | 0.514 | ambiguous | -0.341 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| R/D | 0.9622 | likely_pathogenic | 0.9546 | pathogenic | 0.078 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/E | 0.8243 | likely_pathogenic | 0.8137 | pathogenic | 0.201 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| R/F | 0.8958 | likely_pathogenic | 0.8857 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | I |
| R/G | 0.8186 | likely_pathogenic | 0.7854 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.503623396 | None | None | I |
| R/H | 0.2487 | likely_benign | 0.2314 | benign | -0.968 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| R/I | 0.7258 | likely_pathogenic | 0.7239 | pathogenic | 0.505 | Stabilizing | 1.0 | D | 0.771 | deleterious | N | 0.48541644 | None | None | I |
| R/K | 0.2506 | likely_benign | 0.2355 | benign | -0.256 | Destabilizing | 0.997 | D | 0.569 | neutral | N | 0.463671361 | None | None | I |
| R/L | 0.6502 | likely_pathogenic | 0.6094 | pathogenic | 0.505 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| R/M | 0.812 | likely_pathogenic | 0.7949 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/N | 0.9146 | likely_pathogenic | 0.9007 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| R/P | 0.925 | likely_pathogenic | 0.8621 | pathogenic | 0.274 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/Q | 0.2582 | likely_benign | 0.2456 | benign | -0.035 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| R/S | 0.8786 | likely_pathogenic | 0.8651 | pathogenic | -0.52 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.49358547 | None | None | I |
| R/T | 0.7391 | likely_pathogenic | 0.7301 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.418085918 | None | None | I |
| R/V | 0.7428 | likely_pathogenic | 0.7363 | pathogenic | 0.274 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/W | 0.5359 | ambiguous | 0.5239 | ambiguous | 0.006 | Stabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| R/Y | 0.77 | likely_pathogenic | 0.7629 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
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.