Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14607 | 44044;44045;44046 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| N2AB | 12966 | 39121;39122;39123 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| N2A | 12039 | 36340;36341;36342 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| N2B | 5542 | 16849;16850;16851 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| Novex-1 | 5667 | 17224;17225;17226 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| Novex-2 | 5734 | 17425;17426;17427 | chr2:178631229;178631228;178631227 | chr2:179495956;179495955;179495954 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 1.0 | D | 0.881 | 0.745 | 0.874117924916 | gnomAD-4.0.0 | 1.20032E-06 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| C/Y | rs781427869  |
-1.669 | 1.0 | D | 0.876 | 0.685 | 0.811788188336 | gnomAD-2.1.1 | 1.21E-05 | None | None | disulfide | None | N | None | 0 | 8.72E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/Y | rs781427869 |
-1.669 | 1.0 | D | 0.876 | 0.685 | 0.811788188336 | gnomAD-3.1.2 | 6.58E-06 | None | None | disulfide | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs781427869 |
-1.669 | 1.0 | D | 0.876 | 0.685 | 0.811788188336 | gnomAD-4.0.0 | 5.58056E-06 | None | None | disulfide | None | N | None | 0 | 6.67512E-05 | None | 0 | 0 | None | 0 | 0 | 8.47825E-07 | 0 | 6.40985E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.8064 | likely_pathogenic | 0.8214 | pathogenic | -1.623 | Destabilizing | 0.998 | D | 0.656 | neutral | None | None | disulfide | None | N |
| C/D | 0.9961 | likely_pathogenic | 0.9974 | pathogenic | -1.671 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | disulfide | None | N |
| C/E | 0.998 | likely_pathogenic | 0.9987 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | disulfide | None | N |
| C/F | 0.8925 | likely_pathogenic | 0.9307 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.864 | deleterious | D | 0.788773101 | disulfide | None | N |
| C/G | 0.6116 | likely_pathogenic | 0.6486 | pathogenic | -1.979 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.735055814 | disulfide | None | N |
| C/H | 0.9942 | likely_pathogenic | 0.9962 | pathogenic | -2.218 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | disulfide | None | N |
| C/I | 0.9237 | likely_pathogenic | 0.948 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | disulfide | None | N |
| C/K | 0.9988 | likely_pathogenic | 0.9993 | pathogenic | -1.263 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | disulfide | None | N |
| C/L | 0.897 | likely_pathogenic | 0.9328 | pathogenic | -0.659 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | disulfide | None | N |
| C/M | 0.9493 | likely_pathogenic | 0.9632 | pathogenic | -0.059 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | disulfide | None | N |
| C/N | 0.9861 | likely_pathogenic | 0.9896 | pathogenic | -1.862 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | disulfide | None | N |
| C/P | 0.9983 | likely_pathogenic | 0.999 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | disulfide | None | N |
| C/Q | 0.9961 | likely_pathogenic | 0.9976 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | disulfide | None | N |
| C/R | 0.9886 | likely_pathogenic | 0.9931 | pathogenic | -1.659 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.789909969 | disulfide | None | N |
| C/S | 0.8571 | likely_pathogenic | 0.8693 | pathogenic | -2.151 | Highly Destabilizing | 1.0 | D | 0.794 | deleterious | D | 0.755517005 | disulfide | None | N |
| C/T | 0.8761 | likely_pathogenic | 0.8798 | pathogenic | -1.731 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | disulfide | None | N |
| C/V | 0.817 | likely_pathogenic | 0.846 | pathogenic | -0.958 | Destabilizing | 0.999 | D | 0.764 | deleterious | None | None | disulfide | None | N |
| C/W | 0.9823 | likely_pathogenic | 0.9895 | pathogenic | -1.43 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.789909969 | disulfide | None | N |
| C/Y | 0.9621 | likely_pathogenic | 0.9767 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.876 | deleterious | D | 0.755517005 | disulfide | 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.