Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22525 | 67798;67799;67800 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| N2AB | 20884 | 62875;62876;62877 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| N2A | 19957 | 60094;60095;60096 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| N2B | 13460 | 40603;40604;40605 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| Novex-1 | 13585 | 40978;40979;40980 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| Novex-2 | 13652 | 41179;41180;41181 | chr2:178579624;178579623;178579622 | chr2:179444351;179444350;179444349 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.993 | D | 0.864 | 0.76 | 0.872708619939 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79931E-06 | 0 | 0 |
| A/V | rs781320550  |
-0.735 | 0.977 | D | 0.72 | 0.705 | 0.760880696488 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| A/V | rs781320550 |
-0.735 | 0.977 | D | 0.72 | 0.705 | 0.760880696488 | gnomAD-4.0.0 | 2.73746E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59862E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7561 | likely_pathogenic | 0.7389 | pathogenic | -2.18 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| A/D | 0.9964 | likely_pathogenic | 0.9953 | pathogenic | -3.232 | Highly Destabilizing | 0.993 | D | 0.864 | deleterious | D | 0.634791298 | None | None | N |
| A/E | 0.9917 | likely_pathogenic | 0.9904 | pathogenic | -3.045 | Highly Destabilizing | 0.995 | D | 0.815 | deleterious | None | None | None | None | N |
| A/F | 0.9848 | likely_pathogenic | 0.9853 | pathogenic | -0.858 | Destabilizing | 0.999 | D | 0.905 | deleterious | None | None | None | None | N |
| A/G | 0.4929 | ambiguous | 0.4425 | ambiguous | -1.96 | Destabilizing | 0.955 | D | 0.615 | neutral | D | 0.617157502 | None | None | N |
| A/H | 0.9951 | likely_pathogenic | 0.9938 | pathogenic | -1.809 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| A/I | 0.9437 | likely_pathogenic | 0.9482 | pathogenic | -0.519 | Destabilizing | 0.998 | D | 0.843 | deleterious | None | None | None | None | N |
| A/K | 0.9973 | likely_pathogenic | 0.9969 | pathogenic | -1.528 | Destabilizing | 0.995 | D | 0.813 | deleterious | None | None | None | None | N |
| A/L | 0.8651 | likely_pathogenic | 0.8854 | pathogenic | -0.519 | Destabilizing | 0.983 | D | 0.783 | deleterious | None | None | None | None | N |
| A/M | 0.9247 | likely_pathogenic | 0.9304 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| A/N | 0.9893 | likely_pathogenic | 0.9862 | pathogenic | -2.018 | Highly Destabilizing | 0.995 | D | 0.865 | deleterious | None | None | None | None | N |
| A/P | 0.9328 | likely_pathogenic | 0.8762 | pathogenic | -0.836 | Destabilizing | 0.997 | D | 0.847 | deleterious | D | 0.618166524 | None | None | N |
| A/Q | 0.9825 | likely_pathogenic | 0.9801 | pathogenic | -1.882 | Destabilizing | 0.998 | D | 0.842 | deleterious | None | None | None | None | N |
| A/R | 0.9877 | likely_pathogenic | 0.9875 | pathogenic | -1.463 | Destabilizing | 0.995 | D | 0.853 | deleterious | None | None | None | None | N |
| A/S | 0.3069 | likely_benign | 0.2532 | benign | -2.324 | Highly Destabilizing | 0.568 | D | 0.383 | neutral | D | 0.56965483 | None | None | N |
| A/T | 0.5578 | ambiguous | 0.5296 | ambiguous | -2.032 | Highly Destabilizing | 0.955 | D | 0.661 | neutral | D | 0.617762915 | None | None | N |
| A/V | 0.7221 | likely_pathogenic | 0.7266 | pathogenic | -0.836 | Destabilizing | 0.977 | D | 0.72 | prob.delet. | D | 0.617157502 | None | None | N |
| A/W | 0.9981 | likely_pathogenic | 0.9978 | pathogenic | -1.428 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| A/Y | 0.9941 | likely_pathogenic | 0.9932 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.905 | deleterious | 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.