Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20730 | 62413;62414;62415 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| N2AB | 19089 | 57490;57491;57492 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| N2A | 18162 | 54709;54710;54711 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| N2B | 11665 | 35218;35219;35220 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| Novex-1 | 11790 | 35593;35594;35595 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| Novex-2 | 11857 | 35794;35795;35796 | chr2:178589537;178589536;178589535 | chr2:179454264;179454263;179454262 |
| 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 | rs752344332  |
-2.418 | 0.046 | N | 0.326 | 0.287 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.96104E-04 | None | 0 | 0 | 1.66003E-04 |
| V/A | rs752344332 |
-2.418 | 0.046 | N | 0.326 | 0.287 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| V/A | rs752344332 |
-2.418 | 0.046 | N | 0.326 | 0.287 | None | gnomAD-4.0.0 | 1.11583E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39099E-06 | 1.42754E-04 | 1.60149E-05 |
| V/I | rs1049072812 |
-0.316 | 0.026 | N | 0.283 | 0.13 | 0.522290170867 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs1049072812 |
-0.316 | 0.026 | N | 0.283 | 0.13 | 0.522290170867 | gnomAD-4.0.0 | 4.10619E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.4978E-06 | 1.15955E-05 | 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 | 0.5707 | likely_pathogenic | 0.6318 | pathogenic | -2.003 | Highly Destabilizing | 0.046 | N | 0.326 | neutral | N | 0.476832541 | None | None | N |
| V/C | 0.9518 | likely_pathogenic | 0.9608 | pathogenic | -1.407 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| V/D | 0.9944 | likely_pathogenic | 0.9947 | pathogenic | -3.133 | Highly Destabilizing | 0.984 | D | 0.841 | deleterious | N | 0.488367993 | None | None | N |
| V/E | 0.9815 | likely_pathogenic | 0.9826 | pathogenic | -2.83 | Highly Destabilizing | 0.988 | D | 0.816 | deleterious | None | None | None | None | N |
| V/F | 0.8683 | likely_pathogenic | 0.8849 | pathogenic | -1.205 | Destabilizing | 0.968 | D | 0.789 | deleterious | N | 0.514786679 | None | None | N |
| V/G | 0.9225 | likely_pathogenic | 0.9239 | pathogenic | -2.585 | Highly Destabilizing | 0.896 | D | 0.785 | deleterious | N | 0.518589022 | None | None | N |
| V/H | 0.9958 | likely_pathogenic | 0.9963 | pathogenic | -2.582 | Highly Destabilizing | 0.999 | D | 0.839 | deleterious | None | None | None | None | N |
| V/I | 0.1088 | likely_benign | 0.1331 | benign | -0.32 | Destabilizing | 0.026 | N | 0.283 | neutral | N | 0.506227154 | None | None | N |
| V/K | 0.9923 | likely_pathogenic | 0.9921 | pathogenic | -1.692 | Destabilizing | 0.988 | D | 0.817 | deleterious | None | None | None | None | N |
| V/L | 0.652 | likely_pathogenic | 0.7088 | pathogenic | -0.32 | Destabilizing | 0.64 | D | 0.615 | neutral | N | 0.515958572 | None | None | N |
| V/M | 0.6819 | likely_pathogenic | 0.7623 | pathogenic | -0.451 | Destabilizing | 0.976 | D | 0.672 | neutral | None | None | None | None | N |
| V/N | 0.9839 | likely_pathogenic | 0.9875 | pathogenic | -2.319 | Highly Destabilizing | 0.996 | D | 0.839 | deleterious | None | None | None | None | N |
| V/P | 0.9883 | likely_pathogenic | 0.9873 | pathogenic | -0.861 | Destabilizing | 0.988 | D | 0.823 | deleterious | None | None | None | None | N |
| V/Q | 0.9853 | likely_pathogenic | 0.9852 | pathogenic | -2.004 | Highly Destabilizing | 0.996 | D | 0.818 | deleterious | None | None | None | None | N |
| V/R | 0.9867 | likely_pathogenic | 0.9843 | pathogenic | -1.813 | Destabilizing | 0.988 | D | 0.837 | deleterious | None | None | None | None | N |
| V/S | 0.923 | likely_pathogenic | 0.9304 | pathogenic | -2.806 | Highly Destabilizing | 0.851 | D | 0.771 | deleterious | None | None | None | None | N |
| V/T | 0.7233 | likely_pathogenic | 0.7543 | pathogenic | -2.347 | Highly Destabilizing | 0.919 | D | 0.664 | neutral | None | None | None | None | N |
| V/W | 0.9971 | likely_pathogenic | 0.9978 | pathogenic | -1.834 | Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| V/Y | 0.9889 | likely_pathogenic | 0.9893 | pathogenic | -1.407 | Destabilizing | 0.996 | D | 0.771 | 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.