Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14679 | 44260;44261;44262 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| N2AB | 13038 | 39337;39338;39339 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| N2A | 12111 | 36556;36557;36558 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| N2B | 5614 | 17065;17066;17067 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| Novex-1 | 5739 | 17440;17441;17442 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| Novex-2 | 5806 | 17641;17642;17643 | chr2:178630923;178630922;178630921 | chr2:179495650;179495649;179495648 |
| 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/Q | rs369709751  |
0.407 | 0.999 | N | 0.66 | 0.308 | None | gnomAD-2.1.1 | 1.04341E-04 | None | None | None | None | N | None | 8.28E-05 | 1.43275E-04 | None | 0 | 3.64166E-04 | None | 3.32E-05 | None | 4.01E-05 | 1.02092E-04 | 0 |
| R/Q | rs369709751 |
0.407 | 0.999 | N | 0.66 | 0.308 | None | gnomAD-3.1.2 | 9.87E-05 | None | None | None | None | N | None | 4.83E-05 | 1.96721E-04 | 0 | 0 | 1.94401E-04 | None | 0 | 0 | 1.32376E-04 | 0 | 0 |
| R/Q | rs369709751 |
0.407 | 0.999 | N | 0.66 | 0.308 | None | gnomAD-4.0.0 | 7.26008E-05 | None | None | None | None | N | None | 6.68986E-05 | 1.343E-04 | None | 0 | 2.01387E-04 | None | 0 | 1.64908E-04 | 7.54789E-05 | 1.1038E-05 | 6.41416E-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 | 0.696 | likely_pathogenic | 0.5663 | pathogenic | -0.596 | Destabilizing | 0.982 | D | 0.58 | neutral | None | None | None | None | N |
| R/C | 0.2645 | likely_benign | 0.1951 | benign | -0.545 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/D | 0.8853 | likely_pathogenic | 0.8186 | pathogenic | 0.001 | Stabilizing | 0.997 | D | 0.707 | prob.delet. | None | None | None | None | N |
| R/E | 0.5749 | likely_pathogenic | 0.4879 | ambiguous | 0.138 | Stabilizing | 0.982 | D | 0.533 | neutral | None | None | None | None | N |
| R/F | 0.7382 | likely_pathogenic | 0.6176 | pathogenic | -0.304 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| R/G | 0.5298 | ambiguous | 0.3893 | ambiguous | -0.926 | Destabilizing | 0.995 | D | 0.517 | neutral | N | 0.485554432 | None | None | N |
| R/H | 0.1137 | likely_benign | 0.0952 | benign | -1.263 | Destabilizing | 0.999 | D | 0.686 | prob.delet. | None | None | None | None | N |
| R/I | 0.4912 | ambiguous | 0.3638 | ambiguous | 0.294 | Stabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| R/K | 0.1353 | likely_benign | 0.1177 | benign | -0.678 | Destabilizing | 0.422 | N | 0.33 | neutral | None | None | None | None | N |
| R/L | 0.4299 | ambiguous | 0.3091 | benign | 0.294 | Stabilizing | 0.995 | D | 0.517 | neutral | D | 0.544100989 | None | None | N |
| R/M | 0.5168 | ambiguous | 0.3777 | ambiguous | -0.144 | Destabilizing | 1.0 | D | 0.673 | prob.neutral | None | None | None | None | N |
| R/N | 0.733 | likely_pathogenic | 0.6356 | pathogenic | -0.201 | Destabilizing | 0.997 | D | 0.621 | neutral | None | None | None | None | N |
| R/P | 0.9764 | likely_pathogenic | 0.9474 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.779 | deleterious | D | 0.550580371 | None | None | N |
| R/Q | 0.1366 | likely_benign | 0.1161 | benign | -0.284 | Destabilizing | 0.999 | D | 0.66 | prob.neutral | N | 0.416743294 | None | None | N |
| R/S | 0.6895 | likely_pathogenic | 0.5552 | ambiguous | -0.879 | Destabilizing | 0.982 | D | 0.65 | prob.neutral | None | None | None | None | N |
| R/T | 0.4602 | ambiguous | 0.3324 | benign | -0.554 | Destabilizing | 0.997 | D | 0.6 | neutral | None | None | None | None | N |
| R/V | 0.589 | likely_pathogenic | 0.4881 | ambiguous | 0.019 | Stabilizing | 0.997 | D | 0.741 | deleterious | None | None | None | None | N |
| R/W | 0.3218 | likely_benign | 0.2232 | benign | 0.007 | Stabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| R/Y | 0.5746 | likely_pathogenic | 0.473 | ambiguous | 0.285 | Stabilizing | 0.999 | D | 0.781 | 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.