Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28141 | 84646;84647;84648 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| N2AB | 26500 | 79723;79724;79725 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| N2A | 25573 | 76942;76943;76944 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| N2B | 19076 | 57451;57452;57453 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| Novex-1 | 19201 | 57826;57827;57828 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| Novex-2 | 19268 | 58027;58028;58029 | chr2:178561711;178561710;178561709 | chr2:179426438;179426437;179426436 |
| 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 | 0.061 | N | 0.571 | 0.314 | 0.191931220699 | gnomAD-4.0.0 | 2.74299E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.6046E-06 | 0 | 0 |
| S/I | rs748707866  |
None | None | N | 0.535 | 0.181 | 0.504727117792 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/I | rs748707866 |
None | None | N | 0.535 | 0.181 | 0.504727117792 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | N | None | 2.4122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | None | None | 0.001 | D | 0.554 | 0.353 | 0.299086750705 | gnomAD-4.0.0 | 1.60286E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44001E-05 | 0 |
| S/T | rs748707866 |
-0.866 | 0.001 | N | 0.331 | 0.238 | 0.148003135375 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24442E-04 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs748707866 |
-0.866 | 0.001 | N | 0.331 | 0.238 | 0.148003135375 | gnomAD-4.0.0 | 6.40158E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11383E-04 | None | 0 | 0 | 0 | 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 | 0.0791 | likely_benign | 0.0721 | benign | -0.986 | Destabilizing | 0.001 | N | 0.34 | neutral | None | None | None | None | N |
| S/C | 0.0703 | likely_benign | 0.0625 | benign | -0.766 | Destabilizing | 0.693 | D | 0.727 | prob.delet. | D | 0.528709511 | None | None | N |
| S/D | 0.5585 | ambiguous | 0.497 | ambiguous | -0.993 | Destabilizing | 0.296 | N | 0.617 | neutral | None | None | None | None | N |
| S/E | 0.551 | ambiguous | 0.4788 | ambiguous | -0.873 | Destabilizing | 0.148 | N | 0.59 | neutral | None | None | None | None | N |
| S/F | 0.2098 | likely_benign | 0.2005 | benign | -0.82 | Destabilizing | 0.296 | N | 0.735 | prob.delet. | None | None | None | None | N |
| S/G | 0.1284 | likely_benign | 0.1224 | benign | -1.327 | Destabilizing | 0.061 | N | 0.571 | neutral | N | 0.515832269 | None | None | N |
| S/H | 0.3746 | ambiguous | 0.32 | benign | -1.59 | Destabilizing | 0.749 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/I | 0.1202 | likely_benign | 0.1111 | benign | -0.144 | Destabilizing | None | N | 0.535 | neutral | N | 0.493969032 | None | None | N |
| S/K | 0.6809 | likely_pathogenic | 0.5759 | pathogenic | -0.54 | Destabilizing | 0.08 | N | 0.589 | neutral | None | None | None | None | N |
| S/L | 0.0703 | likely_benign | 0.0686 | benign | -0.144 | Destabilizing | 0.001 | N | 0.567 | neutral | None | None | None | None | N |
| S/M | 0.1756 | likely_benign | 0.158 | benign | -0.164 | Destabilizing | 0.596 | D | 0.731 | prob.delet. | None | None | None | None | N |
| S/N | 0.2125 | likely_benign | 0.1899 | benign | -0.88 | Destabilizing | 0.241 | N | 0.611 | neutral | D | 0.527949043 | None | None | N |
| S/P | 0.7445 | likely_pathogenic | 0.7274 | pathogenic | -0.391 | Destabilizing | 0.46 | N | 0.697 | prob.neutral | None | None | None | None | N |
| S/Q | 0.4892 | ambiguous | 0.4105 | ambiguous | -0.844 | Destabilizing | 0.296 | N | 0.649 | neutral | None | None | None | None | N |
| S/R | 0.5498 | ambiguous | 0.4486 | ambiguous | -0.663 | Destabilizing | 0.001 | N | 0.554 | neutral | D | 0.527188574 | None | None | N |
| S/T | 0.0706 | likely_benign | 0.0654 | benign | -0.738 | Destabilizing | 0.001 | N | 0.331 | neutral | N | 0.507309893 | None | None | N |
| S/V | 0.1257 | likely_benign | 0.1112 | benign | -0.391 | Destabilizing | 0.002 | N | 0.561 | neutral | None | None | None | None | N |
| S/W | 0.3331 | likely_benign | 0.3108 | benign | -0.887 | Destabilizing | 0.972 | D | 0.783 | deleterious | None | None | None | None | N |
| S/Y | 0.1935 | likely_benign | 0.1767 | benign | -0.542 | Destabilizing | 0.46 | N | 0.761 | 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.