Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32934 | 99025;99026;99027 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| N2AB | 31293 | 94102;94103;94104 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| N2A | 30366 | 91321;91322;91323 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| N2B | 23869 | 71830;71831;71832 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| Novex-1 | 23994 | 72205;72206;72207 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| Novex-2 | 24061 | 72406;72407;72408 | chr2:178539135;178539134;178539133 | chr2:179403862;179403861;179403860 |
| 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/L | rs915727477  |
None | 0.689 | N | 0.338 | 0.174 | 0.440604514059 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| I/L | rs915727477 |
None | 0.689 | N | 0.338 | 0.174 | 0.440604514059 | gnomAD-4.0.0 | 6.57315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| I/M | rs1273309840 |
-1.792 | 0.998 | N | 0.639 | 0.335 | 0.437850553699 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| I/M | rs1273309840 |
-1.792 | 0.998 | N | 0.639 | 0.335 | 0.437850553699 | gnomAD-4.0.0 | 6.84226E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99501E-07 | 0 | 0 |
| I/V | rs915727477 |
None | 0.122 | N | 0.243 | 0.094 | 0.428976297845 | gnomAD-4.0.0 | 8.40229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-06 | 0 | 3.66354E-05 |
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 | 0.9151 | likely_pathogenic | 0.9212 | pathogenic | -3.055 | Highly Destabilizing | 0.931 | D | 0.642 | neutral | None | None | None | None | N |
| I/C | 0.9731 | likely_pathogenic | 0.9728 | pathogenic | -2.273 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.529 | Highly Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| I/E | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -3.248 | Highly Destabilizing | 0.999 | D | 0.824 | deleterious | None | None | None | None | N |
| I/F | 0.8894 | likely_pathogenic | 0.9002 | pathogenic | -1.866 | Destabilizing | 0.994 | D | 0.647 | neutral | N | 0.505844045 | None | None | N |
| I/G | 0.9956 | likely_pathogenic | 0.9965 | pathogenic | -3.555 | Highly Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| I/H | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -3.1 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/K | 0.9974 | likely_pathogenic | 0.9979 | pathogenic | -2.552 | Highly Destabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | N |
| I/L | 0.2654 | likely_benign | 0.2836 | benign | -1.511 | Destabilizing | 0.689 | D | 0.338 | neutral | N | 0.447816356 | None | None | N |
| I/M | 0.5013 | ambiguous | 0.4896 | ambiguous | -1.798 | Destabilizing | 0.998 | D | 0.639 | neutral | N | 0.516508437 | None | None | N |
| I/N | 0.9961 | likely_pathogenic | 0.9971 | pathogenic | -3.258 | Highly Destabilizing | 0.998 | D | 0.849 | deleterious | N | 0.506097535 | None | None | N |
| I/P | 0.9963 | likely_pathogenic | 0.9968 | pathogenic | -2.025 | Highly Destabilizing | 0.999 | D | 0.844 | deleterious | None | None | None | None | N |
| I/Q | 0.9975 | likely_pathogenic | 0.9978 | pathogenic | -2.917 | Highly Destabilizing | 0.999 | D | 0.859 | deleterious | None | None | None | None | N |
| I/R | 0.9951 | likely_pathogenic | 0.9962 | pathogenic | -2.565 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| I/S | 0.9851 | likely_pathogenic | 0.9877 | pathogenic | -3.648 | Highly Destabilizing | 0.994 | D | 0.745 | deleterious | N | 0.506097535 | None | None | N |
| I/T | 0.8883 | likely_pathogenic | 0.9038 | pathogenic | -3.23 | Highly Destabilizing | 0.961 | D | 0.615 | neutral | N | 0.505844045 | None | None | N |
| I/V | 0.0846 | likely_benign | 0.0915 | benign | -2.025 | Highly Destabilizing | 0.122 | N | 0.243 | neutral | N | 0.351702813 | None | None | N |
| I/W | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| I/Y | 0.9946 | likely_pathogenic | 0.9955 | pathogenic | -2.079 | Highly Destabilizing | 0.999 | D | 0.732 | prob.delet. | 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.