Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1719 | 5380;5381;5382 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| N2AB | 1719 | 5380;5381;5382 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| N2A | 1719 | 5380;5381;5382 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| N2B | 1673 | 5242;5243;5244 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| Novex-1 | 1673 | 5242;5243;5244 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| Novex-2 | 1673 | 5242;5243;5244 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
| Novex-3 | 1719 | 5380;5381;5382 | chr2:178776709;178776708;178776707 | chr2:179641436;179641435;179641434 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 1.0 | N | 0.812 | 0.532 | 0.796399135963 | gnomAD-4.0.0 | 1.59067E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85651E-06 | 0 | 0 |
| P/S | rs1381415747  |
-0.659 | 1.0 | N | 0.791 | 0.446 | 0.340273420219 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| P/S | rs1381415747 |
-0.659 | 1.0 | N | 0.791 | 0.446 | 0.340273420219 | gnomAD-4.0.0 | 1.3682E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1285 | likely_benign | 0.0993 | benign | -0.47 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.477052756 | None | None | I |
| P/C | 0.8387 | likely_pathogenic | 0.7558 | pathogenic | -0.744 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/D | 0.6769 | likely_pathogenic | 0.5701 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | I |
| P/E | 0.4596 | ambiguous | 0.3601 | ambiguous | -0.115 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| P/F | 0.7181 | likely_pathogenic | 0.5886 | pathogenic | -0.533 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| P/G | 0.5354 | ambiguous | 0.4586 | ambiguous | -0.622 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| P/H | 0.3633 | ambiguous | 0.2714 | benign | -0.046 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.531405233 | None | None | I |
| P/I | 0.521 | ambiguous | 0.3831 | ambiguous | -0.209 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| P/K | 0.5356 | ambiguous | 0.4353 | ambiguous | -0.414 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| P/L | 0.205 | likely_benign | 0.1421 | benign | -0.209 | Destabilizing | 1.0 | D | 0.812 | deleterious | N | 0.507816148 | None | None | I |
| P/M | 0.4959 | ambiguous | 0.3748 | ambiguous | -0.421 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/N | 0.5176 | ambiguous | 0.4044 | ambiguous | -0.252 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| P/Q | 0.2682 | likely_benign | 0.2002 | benign | -0.431 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| P/R | 0.3698 | ambiguous | 0.2908 | benign | 0.065 | Stabilizing | 1.0 | D | 0.827 | deleterious | N | 0.487977493 | None | None | I |
| P/S | 0.2192 | likely_benign | 0.1638 | benign | -0.681 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.442330079 | None | None | I |
| P/T | 0.1932 | likely_benign | 0.1401 | benign | -0.656 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.467785199 | None | None | I |
| P/V | 0.3603 | ambiguous | 0.2598 | benign | -0.262 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| P/W | 0.8848 | likely_pathogenic | 0.8196 | pathogenic | -0.611 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| P/Y | 0.7223 | likely_pathogenic | 0.6151 | pathogenic | -0.321 | Destabilizing | 1.0 | D | 0.798 | 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.