Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23865 | 71818;71819;71820 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| N2AB | 22224 | 66895;66896;66897 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| N2A | 21297 | 64114;64115;64116 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| N2B | 14800 | 44623;44624;44625 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| Novex-1 | 14925 | 44998;44999;45000 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| Novex-2 | 14992 | 45199;45200;45201 | chr2:178574539;178574538;178574537 | chr2:179439266;179439265;179439264 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 1.0 | N | 0.835 | 0.517 | 0.50557994651 | gnomAD-4.0.0 | 1.59169E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-05 | 0 |
| R/I | rs1255670842  |
-0.976 | 1.0 | N | 0.879 | 0.451 | 0.480497669815 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/I | rs1255670842 |
-0.976 | 1.0 | N | 0.879 | 0.451 | 0.480497669815 | gnomAD-4.0.0 | 1.59167E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7889 | likely_pathogenic | 0.7618 | pathogenic | -2.159 | Highly Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/C | 0.1884 | likely_benign | 0.1771 | benign | -1.947 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| R/D | 0.9779 | likely_pathogenic | 0.9737 | pathogenic | -1.126 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| R/E | 0.7473 | likely_pathogenic | 0.7227 | pathogenic | -0.882 | Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | N |
| R/F | 0.7147 | likely_pathogenic | 0.6961 | pathogenic | -1.234 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| R/G | 0.6956 | likely_pathogenic | 0.6453 | pathogenic | -2.523 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.472761136 | None | None | N |
| R/H | 0.1958 | likely_benign | 0.1818 | benign | -1.972 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| R/I | 0.5173 | ambiguous | 0.496 | ambiguous | -1.082 | Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.507608447 | None | None | N |
| R/K | 0.1254 | likely_benign | 0.129 | benign | -1.116 | Destabilizing | 0.997 | D | 0.679 | prob.neutral | N | 0.42687815 | None | None | N |
| R/L | 0.5038 | ambiguous | 0.4927 | ambiguous | -1.082 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| R/M | 0.3995 | ambiguous | 0.3788 | ambiguous | -1.579 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| R/N | 0.9139 | likely_pathogenic | 0.9011 | pathogenic | -1.428 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| R/P | 0.9962 | likely_pathogenic | 0.9955 | pathogenic | -1.433 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| R/Q | 0.1257 | likely_benign | 0.1226 | benign | -1.268 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/S | 0.8447 | likely_pathogenic | 0.8098 | pathogenic | -2.37 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | N | 0.467481217 | None | None | N |
| R/T | 0.6656 | likely_pathogenic | 0.6141 | pathogenic | -1.897 | Destabilizing | 1.0 | D | 0.828 | deleterious | N | 0.472734683 | None | None | N |
| R/V | 0.6087 | likely_pathogenic | 0.5856 | pathogenic | -1.433 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| R/W | 0.2866 | likely_benign | 0.2647 | benign | -0.667 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/Y | 0.4956 | ambiguous | 0.4741 | ambiguous | -0.598 | Destabilizing | 1.0 | D | 0.877 | 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.