Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29859 | 89800;89801;89802 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| N2AB | 28218 | 84877;84878;84879 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| N2A | 27291 | 82096;82097;82098 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| N2B | 20794 | 62605;62606;62607 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| Novex-1 | 20919 | 62980;62981;62982 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| Novex-2 | 20986 | 63181;63182;63183 | chr2:178553325;178553324;178553323 | chr2:179418052;179418051;179418050 |
| 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/L | rs774284668  |
-0.013 | None | N | 0.316 | 0.096 | 0.139678290688 | gnomAD-2.1.1 | 1.82E-05 | None | None | None | None | N | None | 1.65385E-04 | 0 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs774284668 |
-0.013 | None | N | 0.316 | 0.096 | 0.139678290688 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs774284668 |
-0.013 | None | N | 0.316 | 0.096 | 0.139678290688 | gnomAD-4.0.0 | 5.60907E-06 | None | None | None | None | N | None | 1.06789E-04 | 0 | None | 0 | 2.23025E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | None | None | 0.012 | N | 0.445 | 0.05 | 0.230578612272 | gnomAD-4.0.0 | 1.37707E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80092E-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 | 0.7666 | likely_pathogenic | 0.7323 | pathogenic | -1.754 | Destabilizing | None | N | 0.331 | neutral | N | 0.517916733 | None | None | N |
| V/C | 0.8671 | likely_pathogenic | 0.8621 | pathogenic | -1.337 | Destabilizing | 0.824 | D | 0.723 | prob.delet. | None | None | None | None | N |
| V/D | 0.9801 | likely_pathogenic | 0.9773 | pathogenic | -1.953 | Destabilizing | 0.38 | N | 0.821 | deleterious | None | None | None | None | N |
| V/E | 0.9587 | likely_pathogenic | 0.9502 | pathogenic | -1.719 | Destabilizing | 0.317 | N | 0.782 | deleterious | N | 0.483010211 | None | None | N |
| V/F | 0.2446 | likely_benign | 0.2417 | benign | -1.022 | Destabilizing | 0.235 | N | 0.724 | prob.delet. | None | None | None | None | N |
| V/G | 0.8434 | likely_pathogenic | 0.8116 | pathogenic | -2.26 | Highly Destabilizing | 0.062 | N | 0.77 | deleterious | N | 0.483010211 | None | None | N |
| V/H | 0.9719 | likely_pathogenic | 0.9705 | pathogenic | -1.765 | Destabilizing | 0.935 | D | 0.803 | deleterious | None | None | None | None | N |
| V/I | 0.0537 | likely_benign | 0.0609 | benign | -0.343 | Destabilizing | None | N | 0.213 | neutral | None | None | None | None | N |
| V/K | 0.9672 | likely_pathogenic | 0.9625 | pathogenic | -1.491 | Destabilizing | 0.38 | N | 0.786 | deleterious | None | None | None | None | N |
| V/L | 0.1264 | likely_benign | 0.132 | benign | -0.343 | Destabilizing | None | N | 0.316 | neutral | N | 0.296855182 | None | None | N |
| V/M | 0.2161 | likely_benign | 0.2162 | benign | -0.449 | Destabilizing | 0.012 | N | 0.445 | neutral | N | 0.436877004 | None | None | N |
| V/N | 0.9412 | likely_pathogenic | 0.9382 | pathogenic | -1.921 | Destabilizing | 0.555 | D | 0.828 | deleterious | None | None | None | None | N |
| V/P | 0.977 | likely_pathogenic | 0.9744 | pathogenic | -0.788 | Destabilizing | 0.38 | N | 0.807 | deleterious | None | None | None | None | N |
| V/Q | 0.9546 | likely_pathogenic | 0.9466 | pathogenic | -1.689 | Destabilizing | 0.555 | D | 0.81 | deleterious | None | None | None | None | N |
| V/R | 0.9527 | likely_pathogenic | 0.9494 | pathogenic | -1.446 | Destabilizing | 0.38 | N | 0.829 | deleterious | None | None | None | None | N |
| V/S | 0.9099 | likely_pathogenic | 0.903 | pathogenic | -2.546 | Highly Destabilizing | 0.081 | N | 0.732 | prob.delet. | None | None | None | None | N |
| V/T | 0.8838 | likely_pathogenic | 0.8624 | pathogenic | -2.148 | Highly Destabilizing | 0.081 | N | 0.619 | neutral | None | None | None | None | N |
| V/W | 0.9422 | likely_pathogenic | 0.9368 | pathogenic | -1.383 | Destabilizing | 0.935 | D | 0.793 | deleterious | None | None | None | None | N |
| V/Y | 0.8249 | likely_pathogenic | 0.798 | pathogenic | -1.004 | Destabilizing | 0.555 | D | 0.741 | 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.