Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25080 | 75463;75464;75465 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| N2AB | 23439 | 70540;70541;70542 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| N2A | 22512 | 67759;67760;67761 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| N2B | 16015 | 48268;48269;48270 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| Novex-1 | 16140 | 48643;48644;48645 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| Novex-2 | 16207 | 48844;48845;48846 | chr2:178570894;178570893;178570892 | chr2:179435621;179435620;179435619 |
| 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/P | rs543598247  |
-1.498 | 1.0 | D | 0.801 | 0.601 | 0.51627217869 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/P | rs543598247 |
-1.498 | 1.0 | D | 0.801 | 0.601 | 0.51627217869 | gnomAD-4.0.0 | 1.36862E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79918E-06 | 0 | 0 |
| R/Q | rs543598247 |
-1.029 | 1.0 | N | 0.79 | 0.438 | 0.204665344411 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 6.46E-05 | 5.8E-05 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 0 | 2.67E-05 | 0 |
| R/Q | rs543598247 |
-1.029 | 1.0 | N | 0.79 | 0.438 | 0.204665344411 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs543598247 |
-1.029 | 1.0 | N | 0.79 | 0.438 | 0.204665344411 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs543598247 |
-1.029 | 1.0 | N | 0.79 | 0.438 | 0.204665344411 | gnomAD-4.0.0 | 1.67343E-05 | None | None | None | None | N | None | 4.00043E-05 | 1.33369E-04 | None | 0 | 4.46468E-05 | None | 0 | 1.6518E-04 | 4.23875E-06 | 7.68623E-05 | 1.60102E-05 |
| R/W | rs1370877041 |
-0.834 | 1.0 | D | 0.786 | 0.519 | 0.626044160711 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs1370877041 |
-0.834 | 1.0 | D | 0.786 | 0.519 | 0.626044160711 | gnomAD-4.0.0 | 4.79013E-06 | None | None | None | None | N | None | 0 | 2.23644E-05 | None | 0 | 0 | None | 0 | 0 | 4.49792E-06 | 0 | 1.65695E-05 |
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 | 0.9776 | likely_pathogenic | 0.973 | pathogenic | -2.048 | Highly Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/C | 0.5673 | likely_pathogenic | 0.5367 | ambiguous | -1.948 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/D | 0.9967 | likely_pathogenic | 0.9968 | pathogenic | -0.916 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/E | 0.96 | likely_pathogenic | 0.9587 | pathogenic | -0.706 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/F | 0.9823 | likely_pathogenic | 0.9798 | pathogenic | -1.34 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| R/G | 0.9713 | likely_pathogenic | 0.9691 | pathogenic | -2.385 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.546158299 | None | None | N |
| R/H | 0.3077 | likely_benign | 0.2944 | benign | -2.228 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/I | 0.9638 | likely_pathogenic | 0.9543 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/K | 0.5256 | ambiguous | 0.5037 | ambiguous | -1.354 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| R/L | 0.9241 | likely_pathogenic | 0.9066 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.501440639 | None | None | N |
| R/M | 0.9612 | likely_pathogenic | 0.9516 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/N | 0.9821 | likely_pathogenic | 0.9818 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/P | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.801 | deleterious | D | 0.546411789 | None | None | N |
| R/Q | 0.4544 | ambiguous | 0.438 | ambiguous | -1.18 | Destabilizing | 1.0 | D | 0.79 | deleterious | N | 0.492450964 | None | None | N |
| R/S | 0.9787 | likely_pathogenic | 0.9762 | pathogenic | -2.211 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/T | 0.9698 | likely_pathogenic | 0.9625 | pathogenic | -1.789 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/V | 0.9656 | likely_pathogenic | 0.9578 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/W | 0.7557 | likely_pathogenic | 0.7492 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.546158299 | None | None | N |
| R/Y | 0.9277 | likely_pathogenic | 0.9233 | pathogenic | -0.69 | Destabilizing | 1.0 | D | 0.833 | 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.