Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13866 | 41821;41822;41823 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| N2AB | 12225 | 36898;36899;36900 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| N2A | 11298 | 34117;34118;34119 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| N2B | 4801 | 14626;14627;14628 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| Novex-1 | 4926 | 15001;15002;15003 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| Novex-2 | 4993 | 15202;15203;15204 | chr2:178635975;178635974;178635973 | chr2:179500702;179500701;179500700 |
| 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/I | rs375474669  |
-0.174 | 0.999 | N | 0.558 | 0.25 | None | gnomAD-2.1.1 | 9.27E-05 | None | None | None | None | N | None | 8.31E-05 | 1.47293E-04 | None | 0 | 1.03724E-04 | None | 2.84151E-04 | None | 0 | 6.48E-05 | 0 |
| V/I | rs375474669 |
-0.174 | 0.999 | N | 0.558 | 0.25 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 4.83E-05 | 1.96644E-04 | 1.09649E-03 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 2.07211E-04 | 4.78927E-04 |
| V/I | rs375474669 |
-0.174 | 0.999 | N | 0.558 | 0.25 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/I | rs375474669 |
-0.174 | 0.999 | N | 0.558 | 0.25 | None | gnomAD-4.0.0 | 7.8321E-05 | None | None | None | None | N | None | 4.02328E-05 | 1.36874E-04 | None | 0 | 4.49256E-05 | None | 0 | 0 | 7.61217E-05 | 2.14495E-04 | 4.86934E-05 |
| V/L | rs375474669 |
-0.177 | 0.999 | N | 0.601 | 0.329 | 0.411265580357 | gnomAD-2.1.1 | 4.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.25E-06 | 0 |
| V/L | rs375474669 |
-0.177 | 0.999 | N | 0.601 | 0.329 | 0.411265580357 | gnomAD-4.0.0 | 1.3852E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81618E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9114 | likely_pathogenic | 0.9334 | pathogenic | -2.028 | Highly Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.421426024 | None | None | N |
| V/C | 0.9642 | likely_pathogenic | 0.9662 | pathogenic | -1.812 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| V/D | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -2.101 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| V/E | 0.9939 | likely_pathogenic | 0.9944 | pathogenic | -1.957 | Destabilizing | 1.0 | D | 0.907 | deleterious | N | 0.422783594 | None | None | N |
| V/F | 0.9263 | likely_pathogenic | 0.9322 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/G | 0.9474 | likely_pathogenic | 0.9577 | pathogenic | -2.51 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | N | 0.422783594 | None | None | N |
| V/H | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| V/I | 0.1386 | likely_benign | 0.1523 | benign | -0.725 | Destabilizing | 0.999 | D | 0.558 | neutral | N | 0.382505198 | None | None | N |
| V/K | 0.9937 | likely_pathogenic | 0.9943 | pathogenic | -1.661 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| V/L | 0.7191 | likely_pathogenic | 0.7762 | pathogenic | -0.725 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.326523912 | None | None | N |
| V/M | 0.8456 | likely_pathogenic | 0.8665 | pathogenic | -0.819 | Destabilizing | 1.0 | D | 0.671 | prob.neutral | None | None | None | None | N |
| V/N | 0.9944 | likely_pathogenic | 0.995 | pathogenic | -1.775 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| V/P | 0.993 | likely_pathogenic | 0.9928 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| V/Q | 0.9922 | likely_pathogenic | 0.9923 | pathogenic | -1.749 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| V/R | 0.9878 | likely_pathogenic | 0.9884 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| V/S | 0.9797 | likely_pathogenic | 0.9823 | pathogenic | -2.477 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| V/T | 0.937 | likely_pathogenic | 0.9481 | pathogenic | -2.189 | Highly Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | N |
| V/W | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -1.627 | Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| V/Y | 0.9952 | likely_pathogenic | 0.9955 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.835 | 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.