Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25279 | 76060;76061;76062 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| N2AB | 23638 | 71137;71138;71139 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| N2A | 22711 | 68356;68357;68358 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| N2B | 16214 | 48865;48866;48867 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| Novex-1 | 16339 | 49240;49241;49242 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| Novex-2 | 16406 | 49441;49442;49443 | chr2:178570297;178570296;178570295 | chr2:179435024;179435023;179435022 |
| 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/M | rs897348852  |
None | 0.497 | N | 0.615 | 0.271 | 0.626877219219 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/M | rs897348852 |
None | 0.497 | N | 0.615 | 0.271 | 0.626877219219 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs897348852 |
None | 0.497 | N | 0.615 | 0.271 | 0.626877219219 | gnomAD-4.0.0 | 6.57488E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47063E-05 | 0 | 0 |
| I/T | rs748074844 |
-3.603 | 0.124 | N | 0.53 | 0.475 | 0.730295777819 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs748074844 |
-3.603 | 0.124 | N | 0.53 | 0.475 | 0.730295777819 | gnomAD-4.0.0 | 1.59226E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9465 | likely_pathogenic | 0.9633 | pathogenic | -3.254 | Highly Destabilizing | 0.072 | N | 0.585 | neutral | None | None | None | None | N |
| I/C | 0.9294 | likely_pathogenic | 0.956 | pathogenic | -2.518 | Highly Destabilizing | 0.909 | D | 0.744 | deleterious | None | None | None | None | N |
| I/D | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -3.919 | Highly Destabilizing | 0.726 | D | 0.857 | deleterious | None | None | None | None | N |
| I/E | 0.9974 | likely_pathogenic | 0.9982 | pathogenic | -3.636 | Highly Destabilizing | 0.726 | D | 0.841 | deleterious | None | None | None | None | N |
| I/F | 0.7354 | likely_pathogenic | 0.7811 | pathogenic | -2.019 | Highly Destabilizing | 0.567 | D | 0.615 | neutral | None | None | None | None | N |
| I/G | 0.9916 | likely_pathogenic | 0.9946 | pathogenic | -3.771 | Highly Destabilizing | 0.726 | D | 0.819 | deleterious | None | None | None | None | N |
| I/H | 0.9969 | likely_pathogenic | 0.9979 | pathogenic | -3.233 | Highly Destabilizing | 0.968 | D | 0.865 | deleterious | None | None | None | None | N |
| I/K | 0.9942 | likely_pathogenic | 0.9965 | pathogenic | -2.771 | Highly Destabilizing | 0.667 | D | 0.843 | deleterious | N | 0.511877071 | None | None | N |
| I/L | 0.3279 | likely_benign | 0.3851 | ambiguous | -1.671 | Destabilizing | 0.025 | N | 0.255 | neutral | N | 0.501397338 | None | None | N |
| I/M | 0.4126 | ambiguous | 0.4805 | ambiguous | -1.823 | Destabilizing | 0.497 | N | 0.615 | neutral | N | 0.484872046 | None | None | N |
| I/N | 0.9884 | likely_pathogenic | 0.992 | pathogenic | -3.413 | Highly Destabilizing | 0.89 | D | 0.876 | deleterious | None | None | None | None | N |
| I/P | 0.996 | likely_pathogenic | 0.997 | pathogenic | -2.196 | Highly Destabilizing | 0.89 | D | 0.863 | deleterious | None | None | None | None | N |
| I/Q | 0.9953 | likely_pathogenic | 0.9968 | pathogenic | -3.149 | Highly Destabilizing | 0.89 | D | 0.878 | deleterious | None | None | None | None | N |
| I/R | 0.991 | likely_pathogenic | 0.9945 | pathogenic | -2.568 | Highly Destabilizing | 0.667 | D | 0.878 | deleterious | N | 0.511877071 | None | None | N |
| I/S | 0.9793 | likely_pathogenic | 0.9857 | pathogenic | -3.906 | Highly Destabilizing | 0.567 | D | 0.774 | deleterious | None | None | None | None | N |
| I/T | 0.9493 | likely_pathogenic | 0.9669 | pathogenic | -3.492 | Highly Destabilizing | 0.124 | N | 0.53 | neutral | N | 0.488746386 | None | None | N |
| I/V | 0.0822 | likely_benign | 0.0892 | benign | -2.196 | Highly Destabilizing | None | N | 0.193 | neutral | N | 0.329505452 | None | None | N |
| I/W | 0.9963 | likely_pathogenic | 0.9973 | pathogenic | -2.354 | Highly Destabilizing | 0.968 | D | 0.84 | deleterious | None | None | None | None | N |
| I/Y | 0.9788 | likely_pathogenic | 0.9852 | pathogenic | -2.282 | Highly Destabilizing | 0.726 | D | 0.704 | 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.