Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31988 | 96187;96188;96189 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| N2AB | 30347 | 91264;91265;91266 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| N2A | 29420 | 88483;88484;88485 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| N2B | 22923 | 68992;68993;68994 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| Novex-1 | 23048 | 69367;69368;69369 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| Novex-2 | 23115 | 69568;69569;69570 | chr2:178544267;178544266;178544265 | chr2:179408994;179408993;179408992 |
| 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/M | rs756469423  |
-0.822 | 0.988 | N | 0.633 | 0.329 | 0.485275477626 | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 1.02554E-04 | None | 1.30727E-04 | None | 0 | 3.91E-05 | 0 |
| V/M | rs756469423 |
-0.822 | 0.988 | N | 0.633 | 0.329 | 0.485275477626 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 7.24E-05 | 1.30924E-04 | 0 | 0 | 3.84911E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/M | rs756469423 |
-0.822 | 0.988 | N | 0.633 | 0.329 | 0.485275477626 | gnomAD-4.0.0 | 4.09004E-05 | None | None | None | None | N | None | 8.00918E-05 | 3.33378E-05 | None | 0 | 6.6836E-05 | None | 0 | 0 | 3.64488E-05 | 1.20762E-04 | 1.60123E-05 |
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 | 0.2047 | likely_benign | 0.2151 | benign | -1.874 | Destabilizing | 0.454 | N | 0.541 | neutral | N | 0.511753191 | None | None | N |
| V/C | 0.6106 | likely_pathogenic | 0.6022 | pathogenic | -1.519 | Destabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | N |
| V/D | 0.7639 | likely_pathogenic | 0.7614 | pathogenic | -2.103 | Highly Destabilizing | 0.949 | D | 0.745 | deleterious | None | None | None | None | N |
| V/E | 0.452 | ambiguous | 0.4791 | ambiguous | -2.01 | Highly Destabilizing | 0.934 | D | 0.698 | prob.neutral | N | 0.47617918 | None | None | N |
| V/F | 0.2329 | likely_benign | 0.2346 | benign | -1.305 | Destabilizing | 0.949 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/G | 0.3628 | ambiguous | 0.3615 | ambiguous | -2.291 | Highly Destabilizing | 0.934 | D | 0.741 | deleterious | N | 0.501093878 | None | None | N |
| V/H | 0.6889 | likely_pathogenic | 0.7009 | pathogenic | -1.86 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/I | 0.0769 | likely_benign | 0.0795 | benign | -0.775 | Destabilizing | 0.029 | N | 0.122 | neutral | None | None | None | None | N |
| V/K | 0.4149 | ambiguous | 0.4577 | ambiguous | -1.482 | Destabilizing | 0.949 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/L | 0.1957 | likely_benign | 0.2135 | benign | -0.775 | Destabilizing | 0.013 | N | 0.172 | neutral | N | 0.51144376 | None | None | N |
| V/M | 0.1148 | likely_benign | 0.132 | benign | -0.746 | Destabilizing | 0.988 | D | 0.633 | neutral | N | 0.482900717 | None | None | N |
| V/N | 0.4984 | ambiguous | 0.4996 | ambiguous | -1.509 | Destabilizing | 0.949 | D | 0.741 | deleterious | None | None | None | None | N |
| V/P | 0.9692 | likely_pathogenic | 0.9678 | pathogenic | -1.11 | Destabilizing | 0.974 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/Q | 0.3638 | ambiguous | 0.4015 | ambiguous | -1.571 | Destabilizing | 0.974 | D | 0.672 | neutral | None | None | None | None | N |
| V/R | 0.3961 | ambiguous | 0.4157 | ambiguous | -1.091 | Destabilizing | 0.949 | D | 0.752 | deleterious | None | None | None | None | N |
| V/S | 0.2964 | likely_benign | 0.2998 | benign | -2.12 | Highly Destabilizing | 0.728 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/T | 0.1749 | likely_benign | 0.1852 | benign | -1.905 | Destabilizing | 0.067 | N | 0.381 | neutral | None | None | None | None | N |
| V/W | 0.8464 | likely_pathogenic | 0.8443 | pathogenic | -1.628 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| V/Y | 0.5943 | likely_pathogenic | 0.5989 | pathogenic | -1.299 | Destabilizing | 0.991 | D | 0.695 | prob.neutral | 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.