Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28721 | 86386;86387;86388 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| N2AB | 27080 | 81463;81464;81465 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| N2A | 26153 | 78682;78683;78684 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| N2B | 19656 | 59191;59192;59193 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| Novex-1 | 19781 | 59566;59567;59568 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| Novex-2 | 19848 | 59767;59768;59769 | chr2:178559971;178559970;178559969 | chr2:179424698;179424697;179424696 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs186625228  |
-2.146 | 1.0 | D | 0.853 | 0.869 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs186625228 |
-2.146 | 1.0 | D | 0.853 | 0.869 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| Y/H | rs186625228 |
-2.146 | 1.0 | D | 0.853 | 0.869 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9932 | likely_pathogenic | 0.9886 | pathogenic | -2.765 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| Y/C | 0.9421 | likely_pathogenic | 0.9157 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.657613028 | None | None | N |
| Y/D | 0.9935 | likely_pathogenic | 0.9895 | pathogenic | -3.339 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | D | 0.673632389 | None | None | N |
| Y/E | 0.998 | likely_pathogenic | 0.9967 | pathogenic | -3.105 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| Y/F | 0.2452 | likely_benign | 0.2449 | benign | -0.909 | Destabilizing | 0.999 | D | 0.756 | deleterious | D | 0.630258677 | None | None | N |
| Y/G | 0.9858 | likely_pathogenic | 0.9751 | pathogenic | -3.203 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| Y/H | 0.9671 | likely_pathogenic | 0.9564 | pathogenic | -2.091 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.648094277 | None | None | N |
| Y/I | 0.9564 | likely_pathogenic | 0.9349 | pathogenic | -1.305 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| Y/K | 0.9983 | likely_pathogenic | 0.997 | pathogenic | -1.99 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| Y/L | 0.9434 | likely_pathogenic | 0.9175 | pathogenic | -1.305 | Destabilizing | 0.999 | D | 0.822 | deleterious | None | None | None | None | N |
| Y/M | 0.9702 | likely_pathogenic | 0.9607 | pathogenic | -1.099 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| Y/N | 0.9595 | likely_pathogenic | 0.9444 | pathogenic | -2.885 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.673430584 | None | None | N |
| Y/P | 0.9993 | likely_pathogenic | 0.9987 | pathogenic | -1.808 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| Y/Q | 0.9979 | likely_pathogenic | 0.9965 | pathogenic | -2.548 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| Y/R | 0.9953 | likely_pathogenic | 0.9919 | pathogenic | -1.977 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| Y/S | 0.9887 | likely_pathogenic | 0.982 | pathogenic | -3.172 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.673632389 | None | None | N |
| Y/T | 0.9927 | likely_pathogenic | 0.9873 | pathogenic | -2.804 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| Y/V | 0.9293 | likely_pathogenic | 0.9015 | pathogenic | -1.808 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| Y/W | 0.8736 | likely_pathogenic | 0.8601 | pathogenic | -0.212 | 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.