Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14898 | 44917;44918;44919 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| N2AB | 13257 | 39994;39995;39996 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| N2A | 12330 | 37213;37214;37215 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| N2B | 5833 | 17722;17723;17724 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| Novex-1 | 5958 | 18097;18098;18099 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| Novex-2 | 6025 | 18298;18299;18300 | chr2:178624588;178624587;178624586 | chr2:179489315;179489314;179489313 |
| 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/C | None | None | 1.0 | D | 0.826 | 0.656 | 0.657572108434 | gnomAD-4.0.0 | 1.59355E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86252E-06 | 0 | 0 |
| Y/H | rs752146866  |
-2.107 | 1.0 | N | 0.728 | 0.489 | 0.436993770938 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| Y/H | rs752146866 |
-2.107 | 1.0 | N | 0.728 | 0.489 | 0.436993770938 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9058 | likely_pathogenic | 0.835 | pathogenic | -2.632 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| Y/C | 0.4159 | ambiguous | 0.301 | benign | -1.693 | Destabilizing | 1.0 | D | 0.826 | deleterious | D | 0.65688535 | None | None | N |
| Y/D | 0.8954 | likely_pathogenic | 0.8032 | pathogenic | -2.33 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.707429191 | None | None | N |
| Y/E | 0.9407 | likely_pathogenic | 0.8895 | pathogenic | -2.129 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| Y/F | 0.1876 | likely_benign | 0.1681 | benign | -0.846 | Destabilizing | 0.999 | D | 0.507 | neutral | N | 0.497691841 | None | None | N |
| Y/G | 0.8835 | likely_pathogenic | 0.8179 | pathogenic | -3.061 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| Y/H | 0.4115 | ambiguous | 0.2676 | benign | -1.65 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.513862951 | None | None | N |
| Y/I | 0.786 | likely_pathogenic | 0.7171 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| Y/K | 0.9457 | likely_pathogenic | 0.9028 | pathogenic | -1.89 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| Y/L | 0.7742 | likely_pathogenic | 0.7078 | pathogenic | -1.245 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| Y/M | 0.8413 | likely_pathogenic | 0.789 | pathogenic | -1.099 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| Y/N | 0.5791 | likely_pathogenic | 0.4201 | ambiguous | -2.6 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | D | 0.745243375 | None | None | N |
| Y/P | 0.9933 | likely_pathogenic | 0.9883 | pathogenic | -1.716 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| Y/Q | 0.8923 | likely_pathogenic | 0.8038 | pathogenic | -2.309 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| Y/R | 0.8782 | likely_pathogenic | 0.7975 | pathogenic | -1.738 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| Y/S | 0.7796 | likely_pathogenic | 0.641 | pathogenic | -3.091 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | D | 0.655130454 | None | None | N |
| Y/T | 0.8371 | likely_pathogenic | 0.7245 | pathogenic | -2.764 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| Y/V | 0.7022 | likely_pathogenic | 0.6163 | pathogenic | -1.716 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| Y/W | 0.6229 | likely_pathogenic | 0.5522 | ambiguous | -0.213 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.