Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4756 | 14491;14492;14493 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| N2AB | 4439 | 13540;13541;13542 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| N2A | 3512 | 10759;10760;10761 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| N2B | 4393 | 13402;13403;13404 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| Novex-1 | 4518 | 13777;13778;13779 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| Novex-2 | 4585 | 13978;13979;13980 | chr2:178738187;178738186;178738185 | chr2:179602914;179602913;179602912 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.052 | N | 0.51 | 0.144 | 0.199424873507 | gnomAD-4.0.0 | 3.18293E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7167E-06 | 0 | 0 |
| S/N | None | None | 0.117 | N | 0.583 | 0.133 | 0.0297737177859 | gnomAD-4.0.0 | 1.59145E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 0 |
| S/T | None | None | None | N | 0.289 | 0.147 | 0.0297737177859 | gnomAD-4.0.0 | 1.59145E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85834E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1093 | likely_benign | 0.1313 | benign | -1.035 | Destabilizing | 0.001 | N | 0.311 | neutral | None | None | None | None | N |
| S/C | 0.1237 | likely_benign | 0.1593 | benign | -0.84 | Destabilizing | 0.001 | N | 0.473 | neutral | N | 0.495803924 | None | None | N |
| S/D | 0.573 | likely_pathogenic | 0.6503 | pathogenic | -1.33 | Destabilizing | 0.149 | N | 0.565 | neutral | None | None | None | None | N |
| S/E | 0.5987 | likely_pathogenic | 0.6561 | pathogenic | -1.178 | Destabilizing | 0.149 | N | 0.561 | neutral | None | None | None | None | N |
| S/F | 0.1857 | likely_benign | 0.283 | benign | -0.972 | Destabilizing | 0.555 | D | 0.585 | neutral | None | None | None | None | N |
| S/G | 0.1755 | likely_benign | 0.2288 | benign | -1.388 | Destabilizing | 0.052 | N | 0.51 | neutral | N | 0.495023636 | None | None | N |
| S/H | 0.3557 | ambiguous | 0.3824 | ambiguous | -1.649 | Destabilizing | 0.791 | D | 0.619 | neutral | None | None | None | None | N |
| S/I | 0.1633 | likely_benign | 0.2143 | benign | -0.152 | Destabilizing | 0.062 | N | 0.605 | neutral | N | 0.495450725 | None | None | N |
| S/K | 0.7665 | likely_pathogenic | 0.8145 | pathogenic | -0.406 | Destabilizing | 0.002 | N | 0.348 | neutral | None | None | None | None | N |
| S/L | 0.1273 | likely_benign | 0.1685 | benign | -0.152 | Destabilizing | 0.035 | N | 0.583 | neutral | None | None | None | None | N |
| S/M | 0.1943 | likely_benign | 0.2304 | benign | -0.135 | Destabilizing | 0.555 | D | 0.62 | neutral | None | None | None | None | N |
| S/N | 0.1793 | likely_benign | 0.2263 | benign | -0.958 | Destabilizing | 0.117 | N | 0.583 | neutral | N | 0.49444463 | None | None | N |
| S/P | 0.9388 | likely_pathogenic | 0.9531 | pathogenic | -0.413 | Destabilizing | 0.555 | D | 0.607 | neutral | None | None | None | None | N |
| S/Q | 0.5545 | ambiguous | 0.6131 | pathogenic | -0.867 | Destabilizing | 0.38 | N | 0.614 | neutral | None | None | None | None | N |
| S/R | 0.657 | likely_pathogenic | 0.7142 | pathogenic | -0.587 | Destabilizing | 0.062 | N | 0.586 | neutral | N | 0.493098952 | None | None | N |
| S/T | 0.0616 | likely_benign | 0.0617 | benign | -0.739 | Destabilizing | None | N | 0.289 | neutral | N | 0.391881639 | None | None | N |
| S/V | 0.1679 | likely_benign | 0.2124 | benign | -0.413 | Destabilizing | 0.081 | N | 0.601 | neutral | None | None | None | None | N |
| S/W | 0.3573 | ambiguous | 0.468 | ambiguous | -1.095 | Destabilizing | 0.935 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1812 | likely_benign | 0.245 | benign | -0.707 | Destabilizing | 0.555 | D | 0.601 | 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.