Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31825 | 95698;95699;95700 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| N2AB | 30184 | 90775;90776;90777 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| N2A | 29257 | 87994;87995;87996 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| N2B | 22760 | 68503;68504;68505 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| Novex-1 | 22885 | 68878;68879;68880 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| Novex-2 | 22952 | 69079;69080;69081 | chr2:178545637;178545636;178545635 | chr2:179410364;179410363;179410362 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.889 | N | 0.499 | 0.153 | 0.650830185303 | gnomAD-4.0.0 | 1.59137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 0 |
| I/V | rs1393236297  |
-1.361 | 0.333 | N | 0.283 | 0.135 | 0.388653054685 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.69E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1393236297 |
-1.361 | 0.333 | N | 0.283 | 0.135 | 0.388653054685 | gnomAD-4.0.0 | 4.77411E-06 | None | None | None | None | N | None | 0 | 6.85902E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6581 | likely_pathogenic | 0.6575 | pathogenic | -2.621 | Highly Destabilizing | 0.992 | D | 0.575 | neutral | None | None | None | None | N |
| I/C | 0.8188 | likely_pathogenic | 0.8215 | pathogenic | -1.722 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| I/D | 0.9404 | likely_pathogenic | 0.9392 | pathogenic | -2.958 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/E | 0.8955 | likely_pathogenic | 0.8985 | pathogenic | -2.833 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/F | 0.3179 | likely_benign | 0.3062 | benign | -1.635 | Destabilizing | 0.998 | D | 0.566 | neutral | N | 0.50522429 | None | None | N |
| I/G | 0.9026 | likely_pathogenic | 0.8982 | pathogenic | -3.057 | Highly Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/H | 0.7941 | likely_pathogenic | 0.771 | pathogenic | -2.399 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/K | 0.838 | likely_pathogenic | 0.8174 | pathogenic | -2.125 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| I/L | 0.1872 | likely_benign | 0.1871 | benign | -1.39 | Destabilizing | 0.889 | D | 0.499 | neutral | N | 0.468012696 | None | None | N |
| I/M | 0.151 | likely_benign | 0.1482 | benign | -1.144 | Destabilizing | 0.998 | D | 0.592 | neutral | N | 0.496162089 | None | None | N |
| I/N | 0.5577 | ambiguous | 0.5569 | ambiguous | -2.188 | Highly Destabilizing | 0.999 | D | 0.761 | deleterious | N | 0.453795392 | None | None | N |
| I/P | 0.9826 | likely_pathogenic | 0.9779 | pathogenic | -1.78 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/Q | 0.7993 | likely_pathogenic | 0.7843 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/R | 0.7526 | likely_pathogenic | 0.7203 | pathogenic | -1.551 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/S | 0.5531 | ambiguous | 0.5454 | ambiguous | -2.779 | Highly Destabilizing | 0.998 | D | 0.643 | neutral | N | 0.427550153 | None | None | N |
| I/T | 0.3205 | likely_benign | 0.3087 | benign | -2.548 | Highly Destabilizing | 0.989 | D | 0.611 | neutral | N | 0.339141735 | None | None | N |
| I/V | 0.0962 | likely_benign | 0.0946 | benign | -1.78 | Destabilizing | 0.333 | N | 0.283 | neutral | N | 0.37654533 | None | None | N |
| I/W | 0.8935 | likely_pathogenic | 0.8824 | pathogenic | -1.968 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7059 | likely_pathogenic | 0.7074 | pathogenic | -1.774 | Destabilizing | 1.0 | D | 0.657 | 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.