Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2891 | 8896;8897;8898 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| N2AB | 2891 | 8896;8897;8898 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| N2A | 2891 | 8896;8897;8898 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| N2B | 2845 | 8758;8759;8760 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| Novex-1 | 2845 | 8758;8759;8760 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| Novex-2 | 2845 | 8758;8759;8760 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
| Novex-3 | 2891 | 8896;8897;8898 | chr2:178769910;178769909;178769908 | chr2:179634637;179634636;179634635 |
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/M | rs766867322  |
None | 0.99 | N | 0.523 | 0.417 | 0.406120066682 | gnomAD-4.0.0 | 1.36819E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52092E-05 | None | 0 | 0 | 8.99302E-07 | 0 | 0 |
| I/T | rs774651047 |
-1.38 | 0.92 | N | 0.462 | 0.486 | 0.743453827052 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/V | None | None | 0.061 | N | 0.149 | 0.094 | 0.468336420597 | gnomAD-4.0.0 | 1.5906E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85656E-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 | 0.2 | likely_benign | 0.2546 | benign | -1.661 | Destabilizing | 0.079 | N | 0.215 | neutral | None | None | None | None | N |
| I/C | 0.65 | likely_pathogenic | 0.762 | pathogenic | -0.986 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| I/D | 0.7284 | likely_pathogenic | 0.8481 | pathogenic | -0.823 | Destabilizing | 0.991 | D | 0.577 | neutral | None | None | None | None | N |
| I/E | 0.5063 | ambiguous | 0.6065 | pathogenic | -0.77 | Destabilizing | 0.991 | D | 0.564 | neutral | None | None | None | None | N |
| I/F | 0.2101 | likely_benign | 0.2727 | benign | -1.052 | Destabilizing | 0.976 | D | 0.511 | neutral | N | 0.514826976 | None | None | N |
| I/G | 0.6508 | likely_pathogenic | 0.7581 | pathogenic | -2.038 | Highly Destabilizing | 0.939 | D | 0.543 | neutral | None | None | None | None | N |
| I/H | 0.5002 | ambiguous | 0.6359 | pathogenic | -1.248 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| I/K | 0.2775 | likely_benign | 0.3698 | ambiguous | -1.015 | Destabilizing | 0.991 | D | 0.561 | neutral | None | None | None | None | N |
| I/L | 0.1168 | likely_benign | 0.135 | benign | -0.678 | Destabilizing | 0.015 | N | 0.143 | neutral | N | 0.446892744 | None | None | N |
| I/M | 0.081 | likely_benign | 0.089 | benign | -0.574 | Destabilizing | 0.99 | D | 0.523 | neutral | N | 0.51379195 | None | None | N |
| I/N | 0.3301 | likely_benign | 0.4557 | ambiguous | -0.89 | Destabilizing | 0.996 | D | 0.596 | neutral | D | 0.576429977 | None | None | N |
| I/P | 0.8877 | likely_pathogenic | 0.9547 | pathogenic | -0.975 | Destabilizing | 0.991 | D | 0.578 | neutral | None | None | None | None | N |
| I/Q | 0.3475 | ambiguous | 0.4396 | ambiguous | -0.975 | Destabilizing | 0.997 | D | 0.604 | neutral | None | None | None | None | N |
| I/R | 0.2076 | likely_benign | 0.3029 | benign | -0.555 | Destabilizing | 0.991 | D | 0.586 | neutral | None | None | None | None | N |
| I/S | 0.2592 | likely_benign | 0.3457 | ambiguous | -1.595 | Destabilizing | 0.852 | D | 0.479 | neutral | N | 0.515992926 | None | None | N |
| I/T | 0.0867 | likely_benign | 0.1016 | benign | -1.411 | Destabilizing | 0.92 | D | 0.462 | neutral | N | 0.50941196 | None | None | N |
| I/V | 0.0672 | likely_benign | 0.0667 | benign | -0.975 | Destabilizing | 0.061 | N | 0.149 | neutral | N | 0.447307234 | None | None | N |
| I/W | 0.7841 | likely_pathogenic | 0.8683 | pathogenic | -1.161 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| I/Y | 0.5926 | likely_pathogenic | 0.7142 | pathogenic | -0.908 | Destabilizing | 0.997 | D | 0.533 | neutral | 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.