Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24445 | 73558;73559;73560 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| N2AB | 22804 | 68635;68636;68637 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| N2A | 21877 | 65854;65855;65856 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| N2B | 15380 | 46363;46364;46365 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| Novex-1 | 15505 | 46738;46739;46740 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| Novex-2 | 15572 | 46939;46940;46941 | chr2:178572799;178572798;178572797 | chr2:179437526;179437525;179437524 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.999 | N | 0.531 | 0.314 | 0.185906805712 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/I | rs377334665  |
-0.041 | 1.0 | N | 0.805 | 0.384 | None | gnomAD-2.1.1 | 1.00167E-04 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 4E-05 | 2.03826E-04 | 0 |
| T/I | rs377334665 |
-0.041 | 1.0 | N | 0.805 | 0.384 | None | gnomAD-3.1.2 | 1.11822E-04 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.20621E-04 | 0 | 0 |
| T/I | rs377334665 |
-0.041 | 1.0 | N | 0.805 | 0.384 | None | gnomAD-4.0.0 | 2.11985E-04 | None | None | None | None | I | None | 2.67144E-05 | 0 | None | 0 | 0 | None | 3.1248E-05 | 0 | 2.61951E-04 | 0 | 4.64431E-04 |
| T/N | rs377334665 |
-0.724 | 1.0 | N | 0.797 | 0.346 | 0.302793454619 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| T/N | rs377334665 |
-0.724 | 1.0 | N | 0.797 | 0.346 | 0.302793454619 | gnomAD-4.0.0 | 2.05297E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69876E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1408 | likely_benign | 0.1393 | benign | -0.799 | Destabilizing | 0.999 | D | 0.531 | neutral | N | 0.459023477 | None | None | I |
| T/C | 0.656 | likely_pathogenic | 0.6773 | pathogenic | -0.547 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | I |
| T/D | 0.5966 | likely_pathogenic | 0.6243 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| T/E | 0.5993 | likely_pathogenic | 0.6167 | pathogenic | 0.094 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| T/F | 0.6114 | likely_pathogenic | 0.6079 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| T/G | 0.4623 | ambiguous | 0.4847 | ambiguous | -1.075 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| T/H | 0.4916 | ambiguous | 0.5043 | ambiguous | -1.246 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| T/I | 0.429 | ambiguous | 0.4217 | ambiguous | -0.151 | Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.48291463 | None | None | I |
| T/K | 0.6036 | likely_pathogenic | 0.6111 | pathogenic | -0.591 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| T/L | 0.2407 | likely_benign | 0.2327 | benign | -0.151 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| T/M | 0.1649 | likely_benign | 0.1626 | benign | -0.035 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| T/N | 0.1919 | likely_benign | 0.1963 | benign | -0.623 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.46227548 | None | None | I |
| T/P | 0.1587 | likely_benign | 0.1516 | benign | -0.334 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.471543286 | None | None | I |
| T/Q | 0.4217 | ambiguous | 0.4422 | ambiguous | -0.695 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| T/R | 0.5691 | likely_pathogenic | 0.5748 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| T/S | 0.1127 | likely_benign | 0.1186 | benign | -0.954 | Destabilizing | 0.999 | D | 0.526 | neutral | N | 0.4513973 | None | None | I |
| T/V | 0.2834 | likely_benign | 0.2834 | benign | -0.334 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | I |
| T/W | 0.8815 | likely_pathogenic | 0.8909 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| T/Y | 0.6027 | likely_pathogenic | 0.6049 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.837 | 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.