Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19476 | 58651;58652;58653 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| N2AB | 17835 | 53728;53729;53730 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| N2A | 16908 | 50947;50948;50949 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| N2B | 10411 | 31456;31457;31458 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| Novex-1 | 10536 | 31831;31832;31833 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| Novex-2 | 10603 | 32032;32033;32034 | chr2:178593967;178593966;178593965 | chr2:179458694;179458693;179458692 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.999 | D | 0.78 | 0.729 | 0.835424349326 | gnomAD-4.0.0 | 1.59224E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85932E-06 | 0 | 0 |
| V/F | None | None | 1.0 | D | 0.875 | 0.522 | 0.893142227444 | gnomAD-4.0.0 | 6.84388E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99575E-07 | 0 | 0 |
| V/I | rs397517636  |
-0.352 | 0.997 | N | 0.743 | 0.463 | None | gnomAD-2.1.1 | 2.27783E-03 | None | None | None | None | N | None | 4.13E-05 | 5.67E-05 | None | 0 | 5.15E-05 | None | 2.03553E-02 | None | 0 | 0 | 1.68776E-03 |
| V/I | rs397517636 |
-0.352 | 0.997 | N | 0.743 | 0.463 | None | gnomAD-3.1.2 | 6.57497E-04 | None | None | None | None | N | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 0 | 1.98676E-02 | 0 |
| V/I | rs397517636 |
-0.352 | 0.997 | N | 0.743 | 0.463 | None | 1000 genomes | 5.99042E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.07E-02 | None |
| V/I | rs397517636 |
-0.352 | 0.997 | N | 0.743 | 0.463 | None | gnomAD-4.0.0 | 1.12312E-03 | None | None | None | None | N | None | 3.99915E-05 | 3.33611E-05 | None | 0 | 2.23364E-05 | None | 0 | 1.6518E-03 | 6.78179E-06 | 1.89297E-02 | 1.05651E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.88 | likely_pathogenic | 0.8788 | pathogenic | -1.876 | Destabilizing | 0.999 | D | 0.78 | deleterious | D | 0.615964524 | None | None | N |
| V/C | 0.9819 | likely_pathogenic | 0.9816 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| V/D | 0.9973 | likely_pathogenic | 0.9973 | pathogenic | -2.649 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.616569937 | None | None | N |
| V/E | 0.9934 | likely_pathogenic | 0.9934 | pathogenic | -2.587 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/F | 0.9607 | likely_pathogenic | 0.951 | pathogenic | -1.426 | Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.615964524 | None | None | N |
| V/G | 0.9607 | likely_pathogenic | 0.9644 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | D | 0.616569937 | None | None | N |
| V/H | 0.9988 | likely_pathogenic | 0.9986 | pathogenic | -1.63 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| V/I | 0.1304 | likely_benign | 0.1159 | benign | -0.961 | Destabilizing | 0.997 | D | 0.743 | deleterious | N | 0.520892514 | None | None | N |
| V/K | 0.9966 | likely_pathogenic | 0.996 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/L | 0.9209 | likely_pathogenic | 0.8991 | pathogenic | -0.961 | Destabilizing | 0.997 | D | 0.783 | deleterious | D | 0.59792712 | None | None | N |
| V/M | 0.8839 | likely_pathogenic | 0.8559 | pathogenic | -1.096 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| V/N | 0.9906 | likely_pathogenic | 0.9899 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| V/P | 0.9877 | likely_pathogenic | 0.9886 | pathogenic | -1.237 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/Q | 0.9953 | likely_pathogenic | 0.9951 | pathogenic | -1.854 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/R | 0.9924 | likely_pathogenic | 0.9915 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| V/S | 0.9581 | likely_pathogenic | 0.9571 | pathogenic | -2.207 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| V/T | 0.822 | likely_pathogenic | 0.8062 | pathogenic | -2.034 | Highly Destabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | N |
| V/W | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -1.652 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| V/Y | 0.9972 | likely_pathogenic | 0.9965 | pathogenic | -1.345 | Destabilizing | 1.0 | D | 0.879 | 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.