Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29211 | 87856;87857;87858 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| N2AB | 27570 | 82933;82934;82935 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| N2A | 26643 | 80152;80153;80154 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| N2B | 20146 | 60661;60662;60663 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| Novex-1 | 20271 | 61036;61037;61038 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| Novex-2 | 20338 | 61237;61238;61239 | chr2:178557723;178557722;178557721 | chr2:179422450;179422449;179422448 |
| 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/C | rs557805163  |
-1.601 | 1.0 | D | 0.849 | 0.547 | 0.750349235267 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.94E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs557805163 |
-1.601 | 1.0 | D | 0.849 | 0.547 | 0.750349235267 | 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 |
| R/C | rs557805163 |
-1.601 | 1.0 | D | 0.849 | 0.547 | 0.750349235267 | gnomAD-4.0.0 | 9.29499E-06 | None | None | None | None | N | None | 2.66944E-05 | 0 | None | 1.01351E-04 | 0 | None | 0 | 0 | 8.47568E-06 | 0 | 0 |
| R/H | rs370948914 |
-2.288 | 1.0 | D | 0.807 | 0.538 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 0 |
| R/H | rs370948914 |
-2.288 | 1.0 | D | 0.807 | 0.538 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs370948914 |
-2.288 | 1.0 | D | 0.807 | 0.538 | None | gnomAD-4.0.0 | 4.21373E-05 | None | None | None | None | N | None | 6.67379E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.0006E-05 | 2.19621E-05 | 3.20195E-05 |
| R/S | rs557805163 |
-2.064 | 1.0 | N | 0.733 | 0.472 | 0.522611632499 | gnomAD-2.1.1 | 2.85E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.09668E-04 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs557805163 |
-2.064 | 1.0 | N | 0.733 | 0.472 | 0.522611632499 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.71605E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs557805163 |
-2.064 | 1.0 | N | 0.733 | 0.472 | 0.522611632499 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/S | rs557805163 |
-2.064 | 1.0 | N | 0.733 | 0.472 | 0.522611632499 | gnomAD-4.0.0 | 5.57659E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.00579E-04 | None | 0 | 0 | 0 | 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 | 0.9804 | likely_pathogenic | 0.9877 | pathogenic | -1.898 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| R/C | 0.5864 | likely_pathogenic | 0.7039 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.53728548 | None | None | N |
| R/D | 0.9989 | likely_pathogenic | 0.9994 | pathogenic | -1.298 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| R/E | 0.9767 | likely_pathogenic | 0.9868 | pathogenic | -1.065 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| R/F | 0.9937 | likely_pathogenic | 0.9967 | pathogenic | -0.89 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| R/G | 0.9777 | likely_pathogenic | 0.9875 | pathogenic | -2.249 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | D | 0.54377994 | None | None | N |
| R/H | 0.6347 | likely_pathogenic | 0.7701 | pathogenic | -1.97 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.555389735 | None | None | N |
| R/I | 0.9586 | likely_pathogenic | 0.975 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| R/K | 0.5836 | likely_pathogenic | 0.6891 | pathogenic | -1.292 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| R/L | 0.9339 | likely_pathogenic | 0.9577 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.764 | deleterious | D | 0.525929175 | None | None | N |
| R/M | 0.9619 | likely_pathogenic | 0.9801 | pathogenic | -1.389 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| R/N | 0.9952 | likely_pathogenic | 0.9976 | pathogenic | -1.599 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/P | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.555643225 | None | None | N |
| R/Q | 0.4386 | ambiguous | 0.5804 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| R/S | 0.9869 | likely_pathogenic | 0.9928 | pathogenic | -2.318 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.506251076 | None | None | N |
| R/T | 0.9812 | likely_pathogenic | 0.9901 | pathogenic | -1.875 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/V | 0.9644 | likely_pathogenic | 0.9778 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| R/W | 0.9086 | likely_pathogenic | 0.9444 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| R/Y | 0.9762 | likely_pathogenic | 0.9879 | pathogenic | -0.406 | Destabilizing | 1.0 | D | 0.863 | 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.