Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15013 | 45262;45263;45264 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| N2AB | 13372 | 40339;40340;40341 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| N2A | 12445 | 37558;37559;37560 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| N2B | 5948 | 18067;18068;18069 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| Novex-1 | 6073 | 18442;18443;18444 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| Novex-2 | 6140 | 18643;18644;18645 | chr2:178621885;178621884;178621883 | chr2:179486612;179486611;179486610 |
| 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 | 0.893 | 0.797 | 0.730682531328 | gnomAD-4.0.0 | 6.84851E-07 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00027E-07 | 0 | 0 |
| C/S | rs2058346797  |
None | 1.0 | D | 0.818 | 0.767 | 0.772288770895 | gnomAD-3.1.2 | 6.58E-06 | None | None | disulfide | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/S | rs2058346797 |
None | 1.0 | D | 0.818 | 0.767 | 0.772288770895 | gnomAD-4.0.0 | 1.86084E-06 | None | None | disulfide | None | N | None | 1.33651E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69631E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.8813 | likely_pathogenic | 0.877 | pathogenic | -1.234 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | None | None | disulfide | None | N |
| C/D | 0.9992 | likely_pathogenic | 0.9988 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | disulfide | None | N |
| C/E | 0.9994 | likely_pathogenic | 0.999 | pathogenic | -1.148 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | disulfide | None | N |
| C/F | 0.8904 | likely_pathogenic | 0.8069 | pathogenic | -0.725 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.579644018 | disulfide | None | N |
| C/G | 0.8759 | likely_pathogenic | 0.8682 | pathogenic | -1.586 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.756538271 | disulfide | None | N |
| C/H | 0.9974 | likely_pathogenic | 0.996 | pathogenic | -1.871 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | disulfide | None | N |
| C/I | 0.9137 | likely_pathogenic | 0.8606 | pathogenic | -0.276 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | disulfide | None | N |
| C/K | 0.9996 | likely_pathogenic | 0.9993 | pathogenic | -0.665 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | disulfide | None | N |
| C/L | 0.8703 | likely_pathogenic | 0.8046 | pathogenic | -0.276 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | disulfide | None | N |
| C/M | 0.9584 | likely_pathogenic | 0.932 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.835 | deleterious | None | None | disulfide | None | N |
| C/N | 0.9964 | likely_pathogenic | 0.9951 | pathogenic | -1.392 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | disulfide | None | N |
| C/P | 0.9992 | likely_pathogenic | 0.9989 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | disulfide | None | N |
| C/Q | 0.9982 | likely_pathogenic | 0.9974 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | disulfide | None | N |
| C/R | 0.9947 | likely_pathogenic | 0.9918 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.756538271 | disulfide | None | N |
| C/S | 0.9522 | likely_pathogenic | 0.9445 | pathogenic | -1.592 | Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.756538271 | disulfide | None | N |
| C/T | 0.9597 | likely_pathogenic | 0.9496 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | disulfide | None | N |
| C/V | 0.7835 | likely_pathogenic | 0.7099 | pathogenic | -0.574 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | disulfide | None | N |
| C/W | 0.9924 | likely_pathogenic | 0.9842 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.86 | deleterious | D | 0.756538271 | disulfide | None | N |
| C/Y | 0.9828 | likely_pathogenic | 0.9675 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.697927477 | 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.