Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15589 | 46990;46991;46992 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| N2AB | 13948 | 42067;42068;42069 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| N2A | 13021 | 39286;39287;39288 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| N2B | 6524 | 19795;19796;19797 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| Novex-1 | 6649 | 20170;20171;20172 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| Novex-2 | 6716 | 20371;20372;20373 | chr2:178618785;178618784;178618783 | chr2:179483512;179483511;179483510 |
| 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/A | rs760270288  |
-1.946 | 0.998 | N | 0.721 | 0.331 | 0.519351293798 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| V/A | rs760270288 |
-1.946 | 0.998 | N | 0.721 | 0.331 | 0.519351293798 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| V/L | rs2057787860 |
None | 0.981 | N | 0.692 | 0.257 | 0.448000600372 | gnomAD-4.0.0 | 3.19332E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.73161E-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 | 0.4824 | ambiguous | 0.5699 | pathogenic | -1.839 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | N | 0.462070873 | None | None | N |
| V/C | 0.8201 | likely_pathogenic | 0.8512 | pathogenic | -1.309 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/D | 0.9706 | likely_pathogenic | 0.9797 | pathogenic | -2.669 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| V/E | 0.916 | likely_pathogenic | 0.9375 | pathogenic | -2.431 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | N | 0.472151134 | None | None | N |
| V/F | 0.2462 | likely_benign | 0.3097 | benign | -1.068 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/G | 0.7315 | likely_pathogenic | 0.7755 | pathogenic | -2.388 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | N | 0.471918495 | None | None | N |
| V/H | 0.9395 | likely_pathogenic | 0.954 | pathogenic | -2.274 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| V/I | 0.0697 | likely_benign | 0.0763 | benign | -0.302 | Destabilizing | 0.813 | D | 0.357 | neutral | None | None | None | None | N |
| V/K | 0.9193 | likely_pathogenic | 0.9302 | pathogenic | -1.588 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| V/L | 0.2411 | likely_benign | 0.2923 | benign | -0.302 | Destabilizing | 0.981 | D | 0.692 | prob.neutral | N | 0.453766363 | None | None | N |
| V/M | 0.2381 | likely_benign | 0.3172 | benign | -0.339 | Destabilizing | 0.999 | D | 0.797 | deleterious | N | 0.471918495 | None | None | N |
| V/N | 0.886 | likely_pathogenic | 0.917 | pathogenic | -1.974 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| V/P | 0.9743 | likely_pathogenic | 0.9805 | pathogenic | -0.787 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| V/Q | 0.8719 | likely_pathogenic | 0.8896 | pathogenic | -1.784 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| V/R | 0.8936 | likely_pathogenic | 0.9029 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| V/S | 0.713 | likely_pathogenic | 0.772 | pathogenic | -2.535 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| V/T | 0.5439 | ambiguous | 0.6214 | pathogenic | -2.153 | Highly Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | N |
| V/W | 0.9445 | likely_pathogenic | 0.962 | pathogenic | -1.685 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| V/Y | 0.8026 | likely_pathogenic | 0.8388 | pathogenic | -1.225 | Destabilizing | 1.0 | D | 0.851 | 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.