Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24332 | 73219;73220;73221 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| N2AB | 22691 | 68296;68297;68298 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| N2A | 21764 | 65515;65516;65517 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| N2B | 15267 | 46024;46025;46026 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| Novex-1 | 15392 | 46399;46400;46401 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| Novex-2 | 15459 | 46600;46601;46602 | chr2:178573138;178573137;178573136 | chr2:179437865;179437864;179437863 |
| 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/F | rs876658081  |
None | 0.988 | N | 0.866 | 0.379 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/F | rs876658081 |
None | 0.988 | N | 0.866 | 0.379 | None | gnomAD-4.0.0 | 4.95917E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64582E-04 | 3.39117E-06 | 3.29525E-05 | 0 |
| V/I | rs876658081 |
None | 0.067 | N | 0.296 | 0.074 | 0.373715746628 | gnomAD-4.0.0 | 6.84416E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99643E-07 | 0 | 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 | 0.6795 | likely_pathogenic | 0.6492 | pathogenic | -1.389 | Destabilizing | 0.958 | D | 0.594 | neutral | N | 0.469913981 | None | None | N |
| V/C | 0.86 | likely_pathogenic | 0.8694 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| V/D | 0.9656 | likely_pathogenic | 0.9521 | pathogenic | -1.043 | Destabilizing | 0.998 | D | 0.87 | deleterious | N | 0.520372994 | None | None | N |
| V/E | 0.9075 | likely_pathogenic | 0.8953 | pathogenic | -1.019 | Destabilizing | 0.998 | D | 0.863 | deleterious | None | None | None | None | N |
| V/F | 0.5148 | ambiguous | 0.4684 | ambiguous | -0.943 | Destabilizing | 0.988 | D | 0.866 | deleterious | N | 0.493831587 | None | None | N |
| V/G | 0.8188 | likely_pathogenic | 0.7944 | pathogenic | -1.731 | Destabilizing | 0.994 | D | 0.851 | deleterious | N | 0.50800273 | None | None | N |
| V/H | 0.9652 | likely_pathogenic | 0.9573 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/I | 0.0687 | likely_benign | 0.0702 | benign | -0.545 | Destabilizing | 0.067 | N | 0.296 | neutral | N | 0.50684323 | None | None | N |
| V/K | 0.9419 | likely_pathogenic | 0.9351 | pathogenic | -1.2 | Destabilizing | 0.995 | D | 0.863 | deleterious | None | None | None | None | N |
| V/L | 0.3368 | likely_benign | 0.3556 | ambiguous | -0.545 | Destabilizing | 0.618 | D | 0.473 | neutral | N | 0.505669794 | None | None | N |
| V/M | 0.3733 | ambiguous | 0.3695 | ambiguous | -0.495 | Destabilizing | 0.991 | D | 0.793 | deleterious | None | None | None | None | N |
| V/N | 0.9023 | likely_pathogenic | 0.8758 | pathogenic | -1.011 | Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| V/P | 0.8253 | likely_pathogenic | 0.8216 | pathogenic | -0.791 | Destabilizing | 0.998 | D | 0.881 | deleterious | None | None | None | None | N |
| V/Q | 0.9088 | likely_pathogenic | 0.8971 | pathogenic | -1.124 | Destabilizing | 0.998 | D | 0.882 | deleterious | None | None | None | None | N |
| V/R | 0.9279 | likely_pathogenic | 0.9209 | pathogenic | -0.713 | Destabilizing | 0.998 | D | 0.872 | deleterious | None | None | None | None | N |
| V/S | 0.845 | likely_pathogenic | 0.8157 | pathogenic | -1.574 | Destabilizing | 0.995 | D | 0.855 | deleterious | None | None | None | None | N |
| V/T | 0.7469 | likely_pathogenic | 0.698 | pathogenic | -1.427 | Destabilizing | 0.968 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/W | 0.9685 | likely_pathogenic | 0.967 | pathogenic | -1.126 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| V/Y | 0.8919 | likely_pathogenic | 0.8776 | pathogenic | -0.837 | Destabilizing | 0.995 | D | 0.878 | 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.