Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18198 | 54817;54818;54819 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| N2AB | 16557 | 49894;49895;49896 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| N2A | 15630 | 47113;47114;47115 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| N2B | 9133 | 27622;27623;27624 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| Novex-1 | 9258 | 27997;27998;27999 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| Novex-2 | 9325 | 28198;28199;28200 | chr2:178604095;178604094;178604093 | chr2:179468822;179468821;179468820 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs745885044  |
-2.196 | 1.0 | N | 0.838 | 0.539 | 0.749689913766 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs745885044 |
-2.196 | 1.0 | N | 0.838 | 0.539 | 0.749689913766 | gnomAD-4.0.0 | 1.59357E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43447E-05 | 0 |
| I/V | None | None | 0.993 | N | 0.373 | 0.283 | 0.549755530797 | gnomAD-4.0.0 | 2.73854E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59984E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9783 | likely_pathogenic | 0.9565 | pathogenic | -2.296 | Highly Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| I/C | 0.9883 | likely_pathogenic | 0.9799 | pathogenic | -1.504 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| I/D | 0.9992 | likely_pathogenic | 0.9982 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | I |
| I/E | 0.9962 | likely_pathogenic | 0.9939 | pathogenic | -2.165 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| I/F | 0.9536 | likely_pathogenic | 0.9157 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.522890981 | None | None | I |
| I/G | 0.998 | likely_pathogenic | 0.995 | pathogenic | -2.73 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | I |
| I/H | 0.9986 | likely_pathogenic | 0.9971 | pathogenic | -2.05 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| I/K | 0.9958 | likely_pathogenic | 0.9928 | pathogenic | -1.681 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| I/L | 0.5397 | ambiguous | 0.4796 | ambiguous | -1.106 | Destabilizing | 0.993 | D | 0.389 | neutral | N | 0.473996266 | None | None | I |
| I/M | 0.685 | likely_pathogenic | 0.6088 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.532173826 | None | None | I |
| I/N | 0.9879 | likely_pathogenic | 0.9795 | pathogenic | -1.69 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.533187784 | None | None | I |
| I/P | 0.9742 | likely_pathogenic | 0.9669 | pathogenic | -1.477 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
| I/Q | 0.9956 | likely_pathogenic | 0.9924 | pathogenic | -1.771 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| I/R | 0.9941 | likely_pathogenic | 0.9902 | pathogenic | -1.14 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| I/S | 0.9889 | likely_pathogenic | 0.9785 | pathogenic | -2.352 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | N | 0.52107101 | None | None | I |
| I/T | 0.9762 | likely_pathogenic | 0.959 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | N | 0.509550121 | None | None | I |
| I/V | 0.1271 | likely_benign | 0.0941 | benign | -1.477 | Destabilizing | 0.993 | D | 0.373 | neutral | N | 0.509595534 | None | None | I |
| I/W | 0.9991 | likely_pathogenic | 0.9981 | pathogenic | -1.802 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| I/Y | 0.9952 | likely_pathogenic | 0.9909 | pathogenic | -1.555 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | 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.