Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27760 | 83503;83504;83505 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| N2AB | 26119 | 78580;78581;78582 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| N2A | 25192 | 75799;75800;75801 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| N2B | 18695 | 56308;56309;56310 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| Novex-1 | 18820 | 56683;56684;56685 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| Novex-2 | 18887 | 56884;56885;56886 | chr2:178562854;178562853;178562852 | chr2:179427581;179427580;179427579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs200714263  |
0.421 | 1.0 | D | 0.835 | 0.446 | 0.740940019567 | gnomAD-2.1.1 | 2.88E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.3E-05 | 0 |
| N/I | rs200714263 |
0.421 | 1.0 | D | 0.835 | 0.446 | 0.740940019567 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 2.06782E-04 | 0 |
| N/I | rs200714263 |
0.421 | 1.0 | D | 0.835 | 0.446 | 0.740940019567 | gnomAD-4.0.0 | 3.34766E-05 | None | None | None | None | I | None | 2.66567E-05 | 0 | None | 0 | 0 | None | 0 | 1.65017E-04 | 4.15431E-05 | 2.19679E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3872 | ambiguous | 0.3345 | benign | -1.201 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| N/C | 0.4378 | ambiguous | 0.3936 | ambiguous | -0.203 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| N/D | 0.5499 | ambiguous | 0.5025 | ambiguous | -0.356 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.490567855 | None | None | I |
| N/E | 0.859 | likely_pathogenic | 0.8439 | pathogenic | -0.226 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | I |
| N/F | 0.7805 | likely_pathogenic | 0.7374 | pathogenic | -0.852 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| N/G | 0.5449 | ambiguous | 0.4714 | ambiguous | -1.556 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | I |
| N/H | 0.2162 | likely_benign | 0.1947 | benign | -1.036 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.487542889 | None | None | I |
| N/I | 0.3347 | likely_benign | 0.3185 | benign | -0.279 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.53469434 | None | None | I |
| N/K | 0.8219 | likely_pathogenic | 0.8069 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.516356508 | None | None | I |
| N/L | 0.3535 | ambiguous | 0.339 | benign | -0.279 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| N/M | 0.4267 | ambiguous | 0.4063 | ambiguous | 0.09 | Stabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| N/P | 0.7732 | likely_pathogenic | 0.7676 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| N/Q | 0.6777 | likely_pathogenic | 0.6432 | pathogenic | -0.715 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| N/R | 0.8158 | likely_pathogenic | 0.8089 | pathogenic | -0.16 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| N/S | 0.1083 | likely_benign | 0.0873 | benign | -0.943 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.480377066 | None | None | I |
| N/T | 0.1625 | likely_benign | 0.1399 | benign | -0.604 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | N | 0.468506633 | None | None | I |
| N/V | 0.3302 | likely_benign | 0.3105 | benign | -0.558 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| N/W | 0.9145 | likely_pathogenic | 0.9025 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| N/Y | 0.3804 | ambiguous | 0.3302 | benign | -0.315 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.514547914 | None | None | I |
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.