Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25530 | 76813;76814;76815 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| N2AB | 23889 | 71890;71891;71892 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| N2A | 22962 | 69109;69110;69111 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| N2B | 16465 | 49618;49619;49620 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| Novex-1 | 16590 | 49993;49994;49995 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| Novex-2 | 16657 | 50194;50195;50196 | chr2:178569544;178569543;178569542 | chr2:179434271;179434270;179434269 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs184034300  |
-1.382 | 1.0 | D | 0.767 | 0.294 | 0.417208245017 | gnomAD-2.1.1 | 1.79143E-04 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 1.32254E-03 | 7.84E-05 | 7.07014E-04 |
| L/F | rs184034300 |
-1.382 | 1.0 | D | 0.767 | 0.294 | 0.417208245017 | gnomAD-3.1.2 | 1.38167E-04 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 1.41323E-03 | 0 | 5.89E-05 | 0 | 0 |
| L/F | rs184034300 |
-1.382 | 1.0 | D | 0.767 | 0.294 | 0.417208245017 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| L/F | rs184034300 |
-1.382 | 1.0 | D | 0.767 | 0.294 | 0.417208245017 | gnomAD-4.0.0 | 6.84613E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99719E-07 | 0 | 0 |
| L/S | rs1465564864 |
-2.844 | 1.0 | D | 0.843 | 0.766 | 0.905017681694 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/S | rs1465564864 |
-2.844 | 1.0 | D | 0.843 | 0.766 | 0.905017681694 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs1465564864 |
-2.844 | 1.0 | D | 0.843 | 0.766 | 0.905017681694 | gnomAD-4.0.0 | 1.86024E-06 | None | None | None | None | I | None | 0 | 3.34169E-05 | None | 3.38203E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9587 | likely_pathogenic | 0.9568 | pathogenic | -2.201 | Highly Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | I |
| L/C | 0.9026 | likely_pathogenic | 0.9045 | pathogenic | -1.624 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| L/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -2.199 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | I |
| L/E | 0.997 | likely_pathogenic | 0.9969 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| L/F | 0.531 | ambiguous | 0.5434 | ambiguous | -1.361 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.530653957 | None | None | I |
| L/G | 0.9943 | likely_pathogenic | 0.9933 | pathogenic | -2.678 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| L/H | 0.9889 | likely_pathogenic | 0.9877 | pathogenic | -1.91 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| L/I | 0.1088 | likely_benign | 0.1219 | benign | -0.814 | Destabilizing | 0.999 | D | 0.605 | neutral | D | 0.567718909 | None | None | I |
| L/K | 0.9946 | likely_pathogenic | 0.994 | pathogenic | -1.717 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | I |
| L/M | 0.2538 | likely_benign | 0.2488 | benign | -0.883 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| L/N | 0.9956 | likely_pathogenic | 0.9951 | pathogenic | -2.165 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| L/P | 0.9953 | likely_pathogenic | 0.9956 | pathogenic | -1.261 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| L/Q | 0.9877 | likely_pathogenic | 0.9869 | pathogenic | -1.948 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | I |
| L/R | 0.9906 | likely_pathogenic | 0.9898 | pathogenic | -1.612 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| L/S | 0.9936 | likely_pathogenic | 0.9929 | pathogenic | -2.818 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.627524549 | None | None | I |
| L/T | 0.9777 | likely_pathogenic | 0.9772 | pathogenic | -2.425 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| L/V | 0.1925 | likely_benign | 0.2179 | benign | -1.261 | Destabilizing | 0.999 | D | 0.615 | neutral | D | 0.56522406 | None | None | I |
| L/W | 0.9599 | likely_pathogenic | 0.9571 | pathogenic | -1.54 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| L/Y | 0.948 | likely_pathogenic | 0.9423 | pathogenic | -1.298 | Destabilizing | 1.0 | D | 0.79 | 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.