Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21850 | 65773;65774;65775 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| N2AB | 20209 | 60850;60851;60852 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| N2A | 19282 | 58069;58070;58071 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| N2B | 12785 | 38578;38579;38580 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| Novex-1 | 12910 | 38953;38954;38955 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| Novex-2 | 12977 | 39154;39155;39156 | chr2:178583634;178583633;178583632 | chr2:179448361;179448360;179448359 |
| 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 | rs2048279657  |
None | 0.954 | N | 0.789 | 0.277 | 0.326881540566 | gnomAD-4.0.0 | 1.60414E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44781E-05 | 0 |
| D/V | rs372750796 |
0.447 | 0.954 | N | 0.837 | 0.351 | None | gnomAD-2.1.1 | 8.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/V | rs372750796 |
0.447 | 0.954 | N | 0.837 | 0.351 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs372750796 |
0.447 | 0.954 | N | 0.837 | 0.351 | None | gnomAD-4.0.0 | 2.48629E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3987E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.206 | likely_benign | 0.16 | benign | -0.143 | Destabilizing | 0.912 | D | 0.785 | deleterious | N | 0.50600815 | None | None | N |
| D/C | 0.7783 | likely_pathogenic | 0.661 | pathogenic | 0.096 | Stabilizing | 0.998 | D | 0.872 | deleterious | None | None | None | None | N |
| D/E | 0.1885 | likely_benign | 0.1373 | benign | -0.237 | Destabilizing | 0.018 | N | 0.263 | neutral | N | 0.446671845 | None | None | N |
| D/F | 0.7011 | likely_pathogenic | 0.604 | pathogenic | -0.188 | Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | N |
| D/G | 0.2521 | likely_benign | 0.2017 | benign | -0.305 | Destabilizing | 0.856 | D | 0.835 | deleterious | N | 0.51657186 | None | None | N |
| D/H | 0.442 | ambiguous | 0.3576 | ambiguous | 0.062 | Stabilizing | 0.994 | D | 0.834 | deleterious | N | 0.501190831 | None | None | N |
| D/I | 0.4379 | ambiguous | 0.3309 | benign | 0.225 | Stabilizing | 0.982 | D | 0.864 | deleterious | None | None | None | None | N |
| D/K | 0.4767 | ambiguous | 0.3614 | ambiguous | 0.437 | Stabilizing | 0.932 | D | 0.821 | deleterious | None | None | None | None | N |
| D/L | 0.3866 | ambiguous | 0.3187 | benign | 0.225 | Stabilizing | 0.965 | D | 0.825 | deleterious | None | None | None | None | N |
| D/M | 0.7051 | likely_pathogenic | 0.5736 | pathogenic | 0.283 | Stabilizing | 0.998 | D | 0.892 | deleterious | None | None | None | None | N |
| D/N | 0.1593 | likely_benign | 0.1229 | benign | 0.21 | Stabilizing | 0.954 | D | 0.789 | deleterious | N | 0.50358392 | None | None | N |
| D/P | 0.5328 | ambiguous | 0.4565 | ambiguous | 0.124 | Stabilizing | 0.982 | D | 0.836 | deleterious | None | None | None | None | N |
| D/Q | 0.4292 | ambiguous | 0.3242 | benign | 0.222 | Stabilizing | 0.932 | D | 0.763 | deleterious | None | None | None | None | N |
| D/R | 0.5782 | likely_pathogenic | 0.4773 | ambiguous | 0.569 | Stabilizing | 0.965 | D | 0.832 | deleterious | None | None | None | None | N |
| D/S | 0.1572 | likely_benign | 0.1285 | benign | 0.107 | Stabilizing | 0.797 | D | 0.764 | deleterious | None | None | None | None | N |
| D/T | 0.3362 | likely_benign | 0.2459 | benign | 0.232 | Stabilizing | 0.965 | D | 0.825 | deleterious | None | None | None | None | N |
| D/V | 0.2705 | likely_benign | 0.2014 | benign | 0.124 | Stabilizing | 0.954 | D | 0.837 | deleterious | N | 0.461308564 | None | None | N |
| D/W | 0.9438 | likely_pathogenic | 0.9135 | pathogenic | -0.105 | Destabilizing | 0.998 | D | 0.86 | deleterious | None | None | None | None | N |
| D/Y | 0.3635 | ambiguous | 0.3058 | benign | 0.043 | Stabilizing | 0.998 | D | 0.871 | deleterious | N | 0.500176873 | 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.