Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23651 | 71176;71177;71178 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| N2AB | 22010 | 66253;66254;66255 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| N2A | 21083 | 63472;63473;63474 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| N2B | 14586 | 43981;43982;43983 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| Novex-1 | 14711 | 44356;44357;44358 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| Novex-2 | 14778 | 44557;44558;44559 | chr2:178575181;178575180;178575179 | chr2:179439908;179439907;179439906 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.998 | N | 0.799 | 0.57 | 0.6849472881 | gnomAD-4.0.0 | 6.84658E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99777E-07 | 0 | 0 |
| I/S | rs149075285  |
-2.445 | 0.994 | N | 0.768 | 0.51 | None | gnomAD-2.1.1 | 7.9867E-04 | None | None | None | None | N | None | 8.10474E-03 | 5.12091E-04 | None | 0 | 0 | None | 0 | None | 0 | 5.51E-05 | 2.83366E-04 |
| I/S | rs149075285 |
-2.445 | 0.994 | N | 0.768 | 0.51 | None | gnomAD-3.1.2 | 2.42092E-03 | None | None | None | None | N | None | 8.28382E-03 | 8.51789E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 3.83142E-03 |
| I/S | rs149075285 |
-2.445 | 0.994 | N | 0.768 | 0.51 | None | 1000 genomes | 2.39617E-03 | None | None | None | None | N | None | 9.1E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/S | rs149075285 |
-2.445 | 0.994 | N | 0.768 | 0.51 | None | gnomAD-4.0.0 | 4.54514E-04 | None | None | None | None | N | None | 8.37534E-03 | 5.84151E-04 | None | 6.76178E-05 | 0 | None | 0 | 3.30251E-04 | 1.95022E-05 | 0 | 6.88816E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8554 | likely_pathogenic | 0.8765 | pathogenic | -2.443 | Highly Destabilizing | 0.931 | D | 0.645 | neutral | None | None | None | None | N |
| I/C | 0.867 | likely_pathogenic | 0.883 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/D | 0.9961 | likely_pathogenic | 0.9963 | pathogenic | -2.381 | Highly Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| I/E | 0.9877 | likely_pathogenic | 0.9881 | pathogenic | -2.294 | Highly Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| I/F | 0.4175 | ambiguous | 0.4391 | ambiguous | -1.711 | Destabilizing | 0.989 | D | 0.682 | prob.neutral | N | 0.481221562 | None | None | N |
| I/G | 0.977 | likely_pathogenic | 0.9814 | pathogenic | -2.883 | Highly Destabilizing | 0.999 | D | 0.8 | deleterious | None | None | None | None | N |
| I/H | 0.9764 | likely_pathogenic | 0.977 | pathogenic | -2.195 | Highly Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| I/K | 0.9674 | likely_pathogenic | 0.9656 | pathogenic | -1.945 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| I/L | 0.1554 | likely_benign | 0.1542 | benign | -1.232 | Destabilizing | 0.031 | N | 0.257 | neutral | N | 0.432040748 | None | None | N |
| I/M | 0.2044 | likely_benign | 0.2129 | benign | -0.939 | Destabilizing | 0.989 | D | 0.643 | neutral | N | 0.505445216 | None | None | N |
| I/N | 0.9521 | likely_pathogenic | 0.9564 | pathogenic | -1.908 | Destabilizing | 0.998 | D | 0.799 | deleterious | N | 0.490636858 | None | None | N |
| I/P | 0.9907 | likely_pathogenic | 0.992 | pathogenic | -1.61 | Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | N |
| I/Q | 0.9698 | likely_pathogenic | 0.9702 | pathogenic | -1.992 | Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| I/R | 0.9514 | likely_pathogenic | 0.9504 | pathogenic | -1.363 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| I/S | 0.9303 | likely_pathogenic | 0.9398 | pathogenic | -2.567 | Highly Destabilizing | 0.994 | D | 0.768 | deleterious | N | 0.472279113 | None | None | N |
| I/T | 0.851 | likely_pathogenic | 0.8539 | pathogenic | -2.348 | Highly Destabilizing | 0.961 | D | 0.731 | prob.delet. | N | 0.455642889 | None | None | N |
| I/V | 0.0931 | likely_benign | 0.0999 | benign | -1.61 | Destabilizing | 0.122 | N | 0.223 | neutral | N | 0.43679042 | None | None | N |
| I/W | 0.9732 | likely_pathogenic | 0.9722 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| I/Y | 0.8983 | likely_pathogenic | 0.9035 | pathogenic | -1.713 | Destabilizing | 0.999 | D | 0.761 | 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.