Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2997 | 9214;9215;9216 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| N2AB | 2997 | 9214;9215;9216 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| N2A | 2997 | 9214;9215;9216 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| N2B | 2951 | 9076;9077;9078 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| Novex-1 | 2951 | 9076;9077;9078 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| Novex-2 | 2951 | 9076;9077;9078 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
| Novex-3 | 2997 | 9214;9215;9216 | chr2:178768847;178768846;178768845 | chr2:179633574;179633573;179633572 |
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/F | rs879242806  |
None | 0.997 | D | 0.617 | 0.378 | 0.559465614996 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/F | rs879242806 |
None | 0.997 | D | 0.617 | 0.378 | 0.559465614996 | gnomAD-4.0.0 | 1.23915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69489E-06 | 0 | 0 |
| I/M | None | None | 0.997 | N | 0.599 | 0.306 | 0.568465717781 | gnomAD-4.0.0 | 6.84095E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99297E-07 | 0 | 0 |
| I/V | None | None | 0.889 | N | 0.407 | 0.218 | 0.634606890218 | gnomAD-4.0.0 | 9.57734E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52181E-05 | None | 0 | 0 | 1.16909E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8471 | likely_pathogenic | 0.838 | pathogenic | -1.798 | Destabilizing | 0.996 | D | 0.495 | neutral | None | None | None | None | N |
| I/C | 0.8927 | likely_pathogenic | 0.8972 | pathogenic | -1.219 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| I/D | 0.9879 | likely_pathogenic | 0.9859 | pathogenic | -1.304 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/E | 0.9753 | likely_pathogenic | 0.9709 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/F | 0.5131 | ambiguous | 0.4906 | ambiguous | -1.148 | Destabilizing | 0.997 | D | 0.617 | neutral | D | 0.534709501 | None | None | N |
| I/G | 0.9723 | likely_pathogenic | 0.9717 | pathogenic | -2.153 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/H | 0.9516 | likely_pathogenic | 0.9524 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/K | 0.9302 | likely_pathogenic | 0.9296 | pathogenic | -1.155 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| I/L | 0.2811 | likely_benign | 0.2667 | benign | -0.846 | Destabilizing | 0.104 | N | 0.207 | neutral | N | 0.500091579 | None | None | N |
| I/M | 0.311 | likely_benign | 0.2969 | benign | -0.922 | Destabilizing | 0.997 | D | 0.599 | neutral | N | 0.506628126 | None | None | N |
| I/N | 0.8718 | likely_pathogenic | 0.8598 | pathogenic | -1.255 | Destabilizing | 0.999 | D | 0.757 | deleterious | D | 0.578044061 | None | None | N |
| I/P | 0.9758 | likely_pathogenic | 0.977 | pathogenic | -1.139 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/Q | 0.9455 | likely_pathogenic | 0.9436 | pathogenic | -1.282 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/R | 0.9103 | likely_pathogenic | 0.9097 | pathogenic | -0.713 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/S | 0.8668 | likely_pathogenic | 0.8664 | pathogenic | -1.874 | Destabilizing | 0.999 | D | 0.657 | neutral | D | 0.534709501 | None | None | N |
| I/T | 0.7931 | likely_pathogenic | 0.7727 | pathogenic | -1.639 | Destabilizing | 0.998 | D | 0.609 | neutral | N | 0.512271871 | None | None | N |
| I/V | 0.121 | likely_benign | 0.1268 | benign | -1.139 | Destabilizing | 0.889 | D | 0.407 | neutral | N | 0.442155049 | None | None | N |
| I/W | 0.9764 | likely_pathogenic | 0.9786 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8873 | likely_pathogenic | 0.9043 | pathogenic | -0.967 | Destabilizing | 1.0 | D | 0.665 | 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.