Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14568 | 43927;43928;43929 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| N2AB | 12927 | 39004;39005;39006 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| N2A | 12000 | 36223;36224;36225 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| N2B | 5503 | 16732;16733;16734 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| Novex-1 | 5628 | 17107;17108;17109 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| Novex-2 | 5695 | 17308;17309;17310 | chr2:178632192;178632191;178632190 | chr2:179496919;179496918;179496917 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.935 | D | 0.835 | 0.736 | 0.94186883414 | gnomAD-4.0.0 | 1.60354E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8773E-06 | 0 | 0 |
| V/I | rs372384272  |
0.396 | 0.025 | D | 0.392 | 0.29 | None | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 6.83E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs372384272 |
0.396 | 0.025 | D | 0.392 | 0.29 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs372384272 |
0.396 | 0.025 | D | 0.392 | 0.29 | None | gnomAD-4.0.0 | 4.97249E-06 | None | None | None | None | N | None | 1.06866E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4613 | ambiguous | 0.3953 | ambiguous | -2.113 | Highly Destabilizing | 0.025 | N | 0.415 | neutral | N | 0.448230044 | None | None | N |
| V/C | 0.9221 | likely_pathogenic | 0.8991 | pathogenic | -1.278 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| V/D | 0.9886 | likely_pathogenic | 0.9863 | pathogenic | -3.065 | Highly Destabilizing | 0.987 | D | 0.859 | deleterious | None | None | None | None | N |
| V/E | 0.9743 | likely_pathogenic | 0.9729 | pathogenic | -2.747 | Highly Destabilizing | 0.967 | D | 0.839 | deleterious | D | 0.61114707 | None | None | N |
| V/F | 0.6041 | likely_pathogenic | 0.559 | ambiguous | -1.181 | Destabilizing | 0.975 | D | 0.754 | deleterious | None | None | None | None | N |
| V/G | 0.7009 | likely_pathogenic | 0.6663 | pathogenic | -2.704 | Highly Destabilizing | 0.935 | D | 0.835 | deleterious | D | 0.61114707 | None | None | N |
| V/H | 0.9941 | likely_pathogenic | 0.9927 | pathogenic | -2.686 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| V/I | 0.1348 | likely_benign | 0.1266 | benign | -0.386 | Destabilizing | 0.025 | N | 0.392 | neutral | D | 0.531379809 | None | None | N |
| V/K | 0.9876 | likely_pathogenic | 0.987 | pathogenic | -1.572 | Destabilizing | 0.975 | D | 0.841 | deleterious | None | None | None | None | N |
| V/L | 0.5788 | likely_pathogenic | 0.5779 | pathogenic | -0.386 | Destabilizing | 0.369 | N | 0.625 | neutral | D | 0.548580601 | None | None | N |
| V/M | 0.4844 | ambiguous | 0.4731 | ambiguous | -0.593 | Destabilizing | 0.975 | D | 0.675 | neutral | None | None | None | None | N |
| V/N | 0.975 | likely_pathogenic | 0.9692 | pathogenic | -2.269 | Highly Destabilizing | 0.987 | D | 0.851 | deleterious | None | None | None | None | N |
| V/P | 0.9912 | likely_pathogenic | 0.99 | pathogenic | -0.944 | Destabilizing | 0.987 | D | 0.839 | deleterious | None | None | None | None | N |
| V/Q | 0.9789 | likely_pathogenic | 0.9775 | pathogenic | -1.894 | Destabilizing | 0.987 | D | 0.839 | deleterious | None | None | None | None | N |
| V/R | 0.9751 | likely_pathogenic | 0.9737 | pathogenic | -1.764 | Destabilizing | 0.987 | D | 0.847 | deleterious | None | None | None | None | N |
| V/S | 0.8673 | likely_pathogenic | 0.8351 | pathogenic | -2.714 | Highly Destabilizing | 0.95 | D | 0.829 | deleterious | None | None | None | None | N |
| V/T | 0.6635 | likely_pathogenic | 0.6029 | pathogenic | -2.242 | Highly Destabilizing | 0.916 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/W | 0.9923 | likely_pathogenic | 0.9913 | pathogenic | -1.765 | Destabilizing | 0.999 | D | 0.814 | deleterious | None | None | None | None | N |
| V/Y | 0.967 | likely_pathogenic | 0.9568 | pathogenic | -1.415 | Destabilizing | 0.987 | D | 0.739 | prob.delet. | 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.