Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32440 | 97543;97544;97545 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| N2AB | 30799 | 92620;92621;92622 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| N2A | 29872 | 89839;89840;89841 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| N2B | 23375 | 70348;70349;70350 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| Novex-1 | 23500 | 70723;70724;70725 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| Novex-2 | 23567 | 70924;70925;70926 | chr2:178542438;178542437;178542436 | chr2:179407165;179407164;179407163 |
| 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 | rs759932470  |
-1.674 | 1.0 | N | 0.891 | 0.559 | 0.609718080597 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/C | rs759932470 |
-1.674 | 1.0 | N | 0.891 | 0.559 | 0.609718080597 | gnomAD-4.0.0 | 3.42133E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69855E-06 | 1.15939E-05 | 1.65667E-05 |
| R/H | rs750047570 |
-2.253 | 1.0 | N | 0.755 | 0.559 | 0.46512379133 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/H | rs750047570 |
-2.253 | 1.0 | N | 0.755 | 0.559 | 0.46512379133 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs750047570 |
-2.253 | 1.0 | N | 0.755 | 0.559 | 0.46512379133 | gnomAD-4.0.0 | 9.91604E-06 | None | None | None | None | N | None | 6.67539E-05 | 1.66717E-05 | None | 0 | 0 | None | 0 | 0 | 8.47659E-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 | 0.9773 | likely_pathogenic | 0.9674 | pathogenic | -1.905 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| R/C | 0.706 | likely_pathogenic | 0.634 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.891 | deleterious | N | 0.498528848 | None | None | N |
| R/D | 0.9976 | likely_pathogenic | 0.9965 | pathogenic | -0.886 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/E | 0.9717 | likely_pathogenic | 0.9585 | pathogenic | -0.666 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | N |
| R/F | 0.9931 | likely_pathogenic | 0.9894 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/G | 0.9618 | likely_pathogenic | 0.9447 | pathogenic | -2.259 | Highly Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.5237859 | None | None | N |
| R/H | 0.7765 | likely_pathogenic | 0.6967 | pathogenic | -2.041 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.506353208 | None | None | N |
| R/I | 0.9792 | likely_pathogenic | 0.9688 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/K | 0.5836 | likely_pathogenic | 0.4946 | ambiguous | -1.217 | Destabilizing | 0.998 | D | 0.502 | neutral | None | None | None | None | N |
| R/L | 0.9513 | likely_pathogenic | 0.919 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.506402433 | None | None | N |
| R/M | 0.9565 | likely_pathogenic | 0.9362 | pathogenic | -1.376 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/N | 0.9925 | likely_pathogenic | 0.99 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/P | 0.9987 | likely_pathogenic | 0.9983 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.535560279 | None | None | N |
| R/Q | 0.6082 | likely_pathogenic | 0.5095 | ambiguous | -1.078 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/S | 0.9895 | likely_pathogenic | 0.9845 | pathogenic | -2.116 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.467089597 | None | None | N |
| R/T | 0.9835 | likely_pathogenic | 0.9727 | pathogenic | -1.683 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/V | 0.9768 | likely_pathogenic | 0.9667 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| R/W | 0.9099 | likely_pathogenic | 0.8666 | pathogenic | -0.585 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| R/Y | 0.9726 | likely_pathogenic | 0.9599 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.898 | 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.