Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29766 | 89521;89522;89523 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| N2AB | 28125 | 84598;84599;84600 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| N2A | 27198 | 81817;81818;81819 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| N2B | 20701 | 62326;62327;62328 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| Novex-1 | 20826 | 62701;62702;62703 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| Novex-2 | 20893 | 62902;62903;62904 | chr2:178553709;178553708;178553707 | chr2:179418436;179418435;179418434 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs780822733  |
-1.474 | 0.497 | N | 0.783 | 0.221 | 0.563619085548 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/L | rs780822733 |
-0.702 | 0.009 | N | 0.427 | 0.047 | 0.361360026772 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/L | rs780822733 |
-0.702 | 0.009 | N | 0.427 | 0.047 | 0.361360026772 | gnomAD-4.0.0 | 8.895E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16933E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8487 | likely_pathogenic | 0.843 | pathogenic | -1.762 | Destabilizing | 0.104 | N | 0.643 | neutral | N | 0.47498009 | None | None | I |
| V/C | 0.9569 | likely_pathogenic | 0.9545 | pathogenic | -1.267 | Destabilizing | 0.968 | D | 0.741 | deleterious | None | None | None | None | I |
| V/D | 0.9865 | likely_pathogenic | 0.9879 | pathogenic | -1.644 | Destabilizing | 0.667 | D | 0.855 | deleterious | N | 0.488209273 | None | None | I |
| V/E | 0.9627 | likely_pathogenic | 0.967 | pathogenic | -1.627 | Destabilizing | 0.726 | D | 0.835 | deleterious | None | None | None | None | I |
| V/F | 0.825 | likely_pathogenic | 0.815 | pathogenic | -1.386 | Destabilizing | 0.497 | N | 0.783 | deleterious | N | 0.486941825 | None | None | I |
| V/G | 0.9256 | likely_pathogenic | 0.9315 | pathogenic | -2.114 | Highly Destabilizing | 0.667 | D | 0.843 | deleterious | N | 0.508087955 | None | None | I |
| V/H | 0.9913 | likely_pathogenic | 0.9918 | pathogenic | -1.612 | Destabilizing | 0.968 | D | 0.83 | deleterious | None | None | None | None | I |
| V/I | 0.0692 | likely_benign | 0.0656 | benign | -0.879 | Destabilizing | None | N | 0.211 | neutral | N | 0.377715979 | None | None | I |
| V/K | 0.9723 | likely_pathogenic | 0.9757 | pathogenic | -1.481 | Destabilizing | 0.726 | D | 0.838 | deleterious | None | None | None | None | I |
| V/L | 0.4427 | ambiguous | 0.4535 | ambiguous | -0.879 | Destabilizing | 0.009 | N | 0.427 | neutral | N | 0.478019046 | None | None | I |
| V/M | 0.5485 | ambiguous | 0.5265 | ambiguous | -0.645 | Destabilizing | 0.567 | D | 0.65 | neutral | None | None | None | None | I |
| V/N | 0.9482 | likely_pathogenic | 0.9506 | pathogenic | -1.291 | Destabilizing | 0.89 | D | 0.854 | deleterious | None | None | None | None | I |
| V/P | 0.8473 | likely_pathogenic | 0.861 | pathogenic | -1.139 | Destabilizing | 0.89 | D | 0.834 | deleterious | None | None | None | None | I |
| V/Q | 0.9706 | likely_pathogenic | 0.973 | pathogenic | -1.453 | Destabilizing | 0.89 | D | 0.827 | deleterious | None | None | None | None | I |
| V/R | 0.9635 | likely_pathogenic | 0.9692 | pathogenic | -0.923 | Destabilizing | 0.726 | D | 0.856 | deleterious | None | None | None | None | I |
| V/S | 0.9318 | likely_pathogenic | 0.9281 | pathogenic | -1.856 | Destabilizing | 0.726 | D | 0.817 | deleterious | None | None | None | None | I |
| V/T | 0.8455 | likely_pathogenic | 0.8483 | pathogenic | -1.721 | Destabilizing | 0.272 | N | 0.709 | prob.delet. | None | None | None | None | I |
| V/W | 0.9951 | likely_pathogenic | 0.9947 | pathogenic | -1.573 | Destabilizing | 0.968 | D | 0.795 | deleterious | None | None | None | None | I |
| V/Y | 0.9758 | likely_pathogenic | 0.9751 | pathogenic | -1.304 | Destabilizing | 0.726 | D | 0.765 | 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.