Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27839 | 83740;83741;83742 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| N2AB | 26198 | 78817;78818;78819 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| N2A | 25271 | 76036;76037;76038 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| N2B | 18774 | 56545;56546;56547 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| Novex-1 | 18899 | 56920;56921;56922 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| Novex-2 | 18966 | 57121;57122;57123 | chr2:178562617;178562616;178562615 | chr2:179427344;179427343;179427342 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs376820301  |
-0.608 | 0.961 | D | 0.564 | 0.498 | 0.623225470471 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs376820301 |
-0.608 | 0.961 | D | 0.564 | 0.498 | 0.623225470471 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs376820301 |
-0.608 | 0.961 | D | 0.564 | 0.498 | 0.623225470471 | gnomAD-4.0.0 | 1.31442E-05 | None | None | None | None | N | None | 4.82486E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs376820301 |
-1.079 | 0.749 | N | 0.447 | 0.313 | None | gnomAD-2.1.1 | 4.30308E-04 | None | None | None | None | N | None | 1.65824E-04 | 3.17241E-04 | None | 0 | 1.13695E-03 | None | 2.04304E-04 | None | 0 | 5.81999E-04 | 2.8547E-04 |
| R/Q | rs376820301 |
-1.079 | 0.749 | N | 0.447 | 0.313 | None | gnomAD-3.1.2 | 3.74616E-04 | None | None | None | None | N | None | 1.20621E-04 | 7.20839E-04 | 0 | 0 | 9.64134E-04 | None | 0 | 0 | 4.40969E-04 | 4.14422E-04 | 1.91022E-03 |
| R/Q | rs376820301 |
-1.079 | 0.749 | N | 0.447 | 0.313 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs376820301 |
-1.079 | 0.749 | N | 0.447 | 0.313 | None | gnomAD-4.0.0 | 6.05539E-04 | None | None | None | None | N | None | 1.73727E-04 | 3.86997E-04 | None | 0 | 1.36161E-03 | None | 1.56627E-05 | 6.64011E-04 | 6.55022E-04 | 3.22387E-04 | 1.15488E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9883 | likely_pathogenic | 0.9839 | pathogenic | -1.806 | Destabilizing | 0.939 | D | 0.563 | neutral | None | None | None | None | N |
| R/C | 0.7816 | likely_pathogenic | 0.7476 | pathogenic | -1.798 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/D | 0.9984 | likely_pathogenic | 0.998 | pathogenic | -0.974 | Destabilizing | 0.991 | D | 0.593 | neutral | None | None | None | None | N |
| R/E | 0.9781 | likely_pathogenic | 0.9728 | pathogenic | -0.764 | Destabilizing | 0.822 | D | 0.587 | neutral | None | None | None | None | N |
| R/F | 0.9967 | likely_pathogenic | 0.9958 | pathogenic | -0.978 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/G | 0.982 | likely_pathogenic | 0.9775 | pathogenic | -2.142 | Highly Destabilizing | 0.983 | D | 0.564 | neutral | D | 0.558427928 | None | None | N |
| R/H | 0.6343 | likely_pathogenic | 0.5904 | pathogenic | -2.103 | Highly Destabilizing | 0.989 | D | 0.6 | neutral | None | None | None | None | N |
| R/I | 0.9825 | likely_pathogenic | 0.9775 | pathogenic | -0.834 | Destabilizing | 0.989 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/K | 0.5645 | likely_pathogenic | 0.5348 | ambiguous | -1.421 | Destabilizing | 0.431 | N | 0.642 | neutral | None | None | None | None | N |
| R/L | 0.9614 | likely_pathogenic | 0.9498 | pathogenic | -0.834 | Destabilizing | 0.961 | D | 0.564 | neutral | D | 0.522472908 | None | None | N |
| R/M | 0.9831 | likely_pathogenic | 0.9776 | pathogenic | -1.371 | Destabilizing | 0.997 | D | 0.627 | neutral | None | None | None | None | N |
| R/N | 0.9939 | likely_pathogenic | 0.9918 | pathogenic | -1.376 | Destabilizing | 0.991 | D | 0.548 | neutral | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -1.147 | Destabilizing | 0.998 | D | 0.658 | neutral | D | 0.558934907 | None | None | N |
| R/Q | 0.5867 | likely_pathogenic | 0.5345 | ambiguous | -1.165 | Destabilizing | 0.749 | D | 0.447 | neutral | N | 0.49106011 | None | None | N |
| R/S | 0.9896 | likely_pathogenic | 0.9861 | pathogenic | -2.155 | Highly Destabilizing | 0.939 | D | 0.548 | neutral | None | None | None | None | N |
| R/T | 0.9852 | likely_pathogenic | 0.9804 | pathogenic | -1.743 | Destabilizing | 0.991 | D | 0.546 | neutral | None | None | None | None | N |
| R/V | 0.984 | likely_pathogenic | 0.9789 | pathogenic | -1.147 | Destabilizing | 0.97 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/W | 0.9342 | likely_pathogenic | 0.929 | pathogenic | -0.593 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9851 | likely_pathogenic | 0.9824 | pathogenic | -0.43 | Destabilizing | 0.989 | D | 0.683 | 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.