Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29866 | 89821;89822;89823 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| N2AB | 28225 | 84898;84899;84900 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| N2A | 27298 | 82117;82118;82119 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| N2B | 20801 | 62626;62627;62628 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| Novex-1 | 20926 | 63001;63002;63003 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| Novex-2 | 20993 | 63202;63203;63204 | chr2:178553304;178553303;178553302 | chr2:179418031;179418030;179418029 |
| 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 | rs1346127107  |
-0.198 | 1.0 | N | 0.643 | 0.504 | 0.560190409015 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 5.8E-05 | 0 | 0 |
| R/G | rs1346127107 |
-0.198 | 1.0 | N | 0.643 | 0.504 | 0.560190409015 | gnomAD-4.0.0 | 1.60673E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.12152E-05 | 0 | 0 | 0 | 0 |
| R/K | None | None | 0.997 | N | 0.517 | 0.278 | 0.489589578638 | gnomAD-4.0.0 | 1.60661E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85845E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9829 | likely_pathogenic | 0.9834 | pathogenic | 0.05 | Stabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | I |
| R/C | 0.6485 | likely_pathogenic | 0.6319 | pathogenic | -0.239 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| R/D | 0.9928 | likely_pathogenic | 0.9925 | pathogenic | -0.351 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/E | 0.9527 | likely_pathogenic | 0.9505 | pathogenic | -0.317 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/F | 0.9489 | likely_pathogenic | 0.9457 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/G | 0.9751 | likely_pathogenic | 0.976 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.519040911 | None | None | I |
| R/H | 0.377 | ambiguous | 0.3833 | ambiguous | -0.595 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| R/I | 0.8303 | likely_pathogenic | 0.8378 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.527709653 | None | None | I |
| R/K | 0.3807 | ambiguous | 0.4143 | ambiguous | -0.175 | Destabilizing | 0.997 | D | 0.517 | neutral | N | 0.493557007 | None | None | I |
| R/L | 0.8774 | likely_pathogenic | 0.8728 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| R/M | 0.9179 | likely_pathogenic | 0.9182 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/N | 0.9664 | likely_pathogenic | 0.9677 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/P | 0.9979 | likely_pathogenic | 0.9977 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/Q | 0.5037 | ambiguous | 0.5197 | ambiguous | -0.114 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/S | 0.9756 | likely_pathogenic | 0.9761 | pathogenic | -0.221 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.516721868 | None | None | I |
| R/T | 0.9511 | likely_pathogenic | 0.9545 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.671 | neutral | D | 0.525167993 | None | None | I |
| R/V | 0.9102 | likely_pathogenic | 0.9128 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| R/W | 0.6647 | likely_pathogenic | 0.6277 | pathogenic | -0.512 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| R/Y | 0.8472 | likely_pathogenic | 0.8359 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.741 | 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.