Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28091 | 84496;84497;84498 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| N2AB | 26450 | 79573;79574;79575 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| N2A | 25523 | 76792;76793;76794 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| N2B | 19026 | 57301;57302;57303 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| Novex-1 | 19151 | 57676;57677;57678 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| Novex-2 | 19218 | 57877;57878;57879 | chr2:178561861;178561860;178561859 | chr2:179426588;179426587;179426586 |
| 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/T | None | None | 0.505 | N | 0.711 | 0.275 | 0.671345282208 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| I/V | rs886042615  |
-2.07 | None | N | 0.185 | 0.04 | 0.39843156188 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| I/V | rs886042615 |
-2.07 | None | N | 0.185 | 0.04 | 0.39843156188 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs886042615 |
-2.07 | None | N | 0.185 | 0.04 | 0.39843156188 | gnomAD-4.0.0 | 3.71847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.12471E-05 | 0 | 8.47626E-07 | 2.19578E-05 | 1.60138E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.473 | ambiguous | 0.4163 | ambiguous | -3.033 | Highly Destabilizing | 0.218 | N | 0.69 | prob.neutral | None | None | None | None | N |
| I/C | 0.7835 | likely_pathogenic | 0.7219 | pathogenic | -2.307 | Highly Destabilizing | 0.973 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/D | 0.9236 | likely_pathogenic | 0.8791 | pathogenic | -3.59 | Highly Destabilizing | 0.967 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/E | 0.8144 | likely_pathogenic | 0.7428 | pathogenic | -3.369 | Highly Destabilizing | 0.906 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/F | 0.2829 | likely_benign | 0.2503 | benign | -1.766 | Destabilizing | 0.782 | D | 0.725 | prob.delet. | N | 0.490687581 | None | None | N |
| I/G | 0.8967 | likely_pathogenic | 0.8346 | pathogenic | -3.533 | Highly Destabilizing | 0.906 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/H | 0.6713 | likely_pathogenic | 0.599 | pathogenic | -2.894 | Highly Destabilizing | 0.991 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/K | 0.6114 | likely_pathogenic | 0.4985 | ambiguous | -2.393 | Highly Destabilizing | 0.906 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/L | 0.2057 | likely_benign | 0.1855 | benign | -1.561 | Destabilizing | 0.084 | N | 0.399 | neutral | N | 0.475101313 | None | None | N |
| I/M | 0.1555 | likely_benign | 0.1397 | benign | -1.594 | Destabilizing | 0.782 | D | 0.703 | prob.neutral | N | 0.504779364 | None | None | N |
| I/N | 0.5664 | likely_pathogenic | 0.4762 | ambiguous | -2.774 | Highly Destabilizing | 0.957 | D | 0.735 | prob.delet. | N | 0.485621471 | None | None | N |
| I/P | 0.9884 | likely_pathogenic | 0.9856 | pathogenic | -2.039 | Highly Destabilizing | 0.967 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/Q | 0.6767 | likely_pathogenic | 0.5929 | pathogenic | -2.641 | Highly Destabilizing | 0.967 | D | 0.749 | deleterious | None | None | None | None | N |
| I/R | 0.4651 | ambiguous | 0.3619 | ambiguous | -1.994 | Destabilizing | 0.906 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/S | 0.444 | ambiguous | 0.3761 | ambiguous | -3.378 | Highly Destabilizing | 0.782 | D | 0.698 | prob.neutral | N | 0.472174798 | None | None | N |
| I/T | 0.1664 | likely_benign | 0.1473 | benign | -3.035 | Highly Destabilizing | 0.505 | D | 0.711 | prob.delet. | N | 0.466694296 | None | None | N |
| I/V | 0.0743 | likely_benign | 0.0692 | benign | -2.039 | Highly Destabilizing | None | N | 0.185 | neutral | N | 0.464049671 | None | None | N |
| I/W | 0.8656 | likely_pathogenic | 0.8396 | pathogenic | -2.177 | Highly Destabilizing | 0.991 | D | 0.728 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6922 | likely_pathogenic | 0.6212 | pathogenic | -2.019 | Highly Destabilizing | 0.906 | D | 0.713 | 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.