Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15190 | 45793;45794;45795 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| N2AB | 13549 | 40870;40871;40872 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| N2A | 12622 | 38089;38090;38091 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| N2B | 6125 | 18598;18599;18600 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| Novex-1 | 6250 | 18973;18974;18975 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| Novex-2 | 6317 | 19174;19175;19176 | chr2:178621150;178621149;178621148 | chr2:179485877;179485876;179485875 |
| 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 | rs769206817  |
-2.229 | 0.026 | N | 0.341 | 0.115 | 0.445410361449 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.93E-06 | 0 |
| V/A | rs769206817 |
-2.229 | 0.026 | N | 0.341 | 0.115 | 0.445410361449 | gnomAD-4.0.0 | 3.42326E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69936E-06 | 2.32002E-05 | 0 |
| V/I | rs776996868 |
-0.51 | 0.98 | N | 0.648 | 0.083 | 0.317958651998 | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63538E-04 | None | 0 | 2.68E-05 | 0 |
| V/I | rs776996868 |
-0.51 | 0.98 | N | 0.648 | 0.083 | 0.317958651998 | gnomAD-4.0.0 | 1.30086E-05 | None | None | None | None | N | None | 2.99365E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6994E-06 | 1.74006E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2515 | likely_benign | 0.2662 | benign | -1.665 | Destabilizing | 0.026 | N | 0.341 | neutral | N | 0.450844593 | None | None | N |
| V/C | 0.8425 | likely_pathogenic | 0.8017 | pathogenic | -1.049 | Destabilizing | 0.997 | D | 0.767 | deleterious | None | None | None | None | N |
| V/D | 0.601 | likely_pathogenic | 0.6428 | pathogenic | -2.127 | Highly Destabilizing | 0.968 | D | 0.838 | deleterious | N | 0.503874836 | None | None | N |
| V/E | 0.4523 | ambiguous | 0.4418 | ambiguous | -1.923 | Destabilizing | 0.976 | D | 0.785 | deleterious | None | None | None | None | N |
| V/F | 0.2555 | likely_benign | 0.2767 | benign | -0.952 | Destabilizing | 0.994 | D | 0.795 | deleterious | N | 0.451417084 | None | None | N |
| V/G | 0.4355 | ambiguous | 0.456 | ambiguous | -2.189 | Highly Destabilizing | 0.811 | D | 0.797 | deleterious | N | 0.503874836 | None | None | N |
| V/H | 0.7131 | likely_pathogenic | 0.7068 | pathogenic | -2.002 | Highly Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| V/I | 0.0911 | likely_benign | 0.0963 | benign | -0.222 | Destabilizing | 0.98 | D | 0.648 | neutral | N | 0.447082819 | None | None | N |
| V/K | 0.651 | likely_pathogenic | 0.6126 | pathogenic | -1.32 | Destabilizing | 0.976 | D | 0.779 | deleterious | None | None | None | None | N |
| V/L | 0.3197 | likely_benign | 0.3219 | benign | -0.222 | Destabilizing | 0.819 | D | 0.684 | prob.neutral | N | 0.449456276 | None | None | N |
| V/M | 0.1925 | likely_benign | 0.2052 | benign | -0.19 | Destabilizing | 0.996 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/N | 0.4435 | ambiguous | 0.5115 | ambiguous | -1.581 | Destabilizing | 0.976 | D | 0.855 | deleterious | None | None | None | None | N |
| V/P | 0.9819 | likely_pathogenic | 0.9843 | pathogenic | -0.674 | Destabilizing | 0.988 | D | 0.802 | deleterious | None | None | None | None | N |
| V/Q | 0.5082 | ambiguous | 0.4959 | ambiguous | -1.437 | Destabilizing | 0.988 | D | 0.799 | deleterious | None | None | None | None | N |
| V/R | 0.5799 | likely_pathogenic | 0.5292 | ambiguous | -1.207 | Destabilizing | 0.988 | D | 0.857 | deleterious | None | None | None | None | N |
| V/S | 0.3017 | likely_benign | 0.328 | benign | -2.182 | Highly Destabilizing | 0.851 | D | 0.777 | deleterious | None | None | None | None | N |
| V/T | 0.2049 | likely_benign | 0.2225 | benign | -1.835 | Destabilizing | 0.06 | N | 0.304 | neutral | None | None | None | None | N |
| V/W | 0.9146 | likely_pathogenic | 0.9009 | pathogenic | -1.499 | Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| V/Y | 0.7033 | likely_pathogenic | 0.6911 | pathogenic | -1.043 | Destabilizing | 0.996 | D | 0.789 | 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.