Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33025 | 99298;99299;99300 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| N2AB | 31384 | 94375;94376;94377 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| N2A | 30457 | 91594;91595;91596 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| N2B | 23960 | 72103;72104;72105 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| Novex-1 | 24085 | 72478;72479;72480 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| Novex-2 | 24152 | 72679;72680;72681 | chr2:178538756;178538755;178538754 | chr2:179403483;179403482;179403481 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs878998371  |
-0.194 | 1.0 | N | 0.721 | 0.414 | 0.315903272564 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| D/N | rs878998371 |
-0.194 | 1.0 | N | 0.721 | 0.414 | 0.315903272564 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| D/N | rs878998371 |
-0.194 | 1.0 | N | 0.721 | 0.414 | 0.315903272564 | gnomAD-4.0.0 | 4.58604E-05 | None | None | None | None | N | None | 1.33508E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.10316E-05 | 0 | 1.60123E-05 |
| D/Y | rs878998371 |
None | 1.0 | D | 0.707 | 0.452 | 0.739189542959 | gnomAD-4.0.0 | 3.42127E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59811E-06 | 0 | 1.65651E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6973 | likely_pathogenic | 0.7306 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.496020406 | None | None | N |
| D/C | 0.9241 | likely_pathogenic | 0.9354 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/E | 0.6469 | likely_pathogenic | 0.6996 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.449 | neutral | N | 0.496323121 | None | None | N |
| D/F | 0.9464 | likely_pathogenic | 0.9557 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/G | 0.6771 | likely_pathogenic | 0.7071 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.514328925 | None | None | N |
| D/H | 0.7765 | likely_pathogenic | 0.7935 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.513568457 | None | None | N |
| D/I | 0.9001 | likely_pathogenic | 0.927 | pathogenic | 0.231 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| D/K | 0.9231 | likely_pathogenic | 0.9373 | pathogenic | 0.228 | Stabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| D/L | 0.8866 | likely_pathogenic | 0.914 | pathogenic | 0.231 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/M | 0.9606 | likely_pathogenic | 0.9732 | pathogenic | 0.58 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/N | 0.1466 | likely_benign | 0.1884 | benign | -0.009 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.482284244 | None | None | N |
| D/P | 0.9147 | likely_pathogenic | 0.9299 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| D/Q | 0.8792 | likely_pathogenic | 0.9077 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| D/R | 0.9143 | likely_pathogenic | 0.9288 | pathogenic | 0.202 | Stabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| D/S | 0.3332 | likely_benign | 0.3889 | ambiguous | -0.136 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/T | 0.6235 | likely_pathogenic | 0.7285 | pathogenic | 0.038 | Stabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| D/V | 0.8081 | likely_pathogenic | 0.8471 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.75 | deleterious | N | 0.509769795 | None | None | N |
| D/W | 0.9884 | likely_pathogenic | 0.9901 | pathogenic | -0.342 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/Y | 0.7373 | likely_pathogenic | 0.7651 | pathogenic | -0.195 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | D | 0.550537435 | 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.