Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21037 | 63334;63335;63336 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| N2AB | 19396 | 58411;58412;58413 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| N2A | 18469 | 55630;55631;55632 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| N2B | 11972 | 36139;36140;36141 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| Novex-1 | 12097 | 36514;36515;36516 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| Novex-2 | 12164 | 36715;36716;36717 | chr2:178588616;178588615;178588614 | chr2:179453343;179453342;179453341 |
| 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 | rs191549948  |
-1.456 | 1.0 | N | 0.795 | 0.538 | None | gnomAD-2.1.1 | 1.93998E-04 | None | None | None | None | N | None | 0 | 5.48422E-04 | None | 8.28598E-04 | 0 | None | 2.81283E-04 | None | 0 | 1.07979E-04 | 9.2564E-04 |
| R/C | rs191549948 |
-1.456 | 1.0 | N | 0.795 | 0.538 | None | gnomAD-3.1.2 | 1.97413E-04 | None | None | None | None | N | None | 0 | 1.37831E-03 | 0 | 1.15207E-03 | 0 | None | 0 | 0 | 4.41E-05 | 2.07383E-04 | 4.78469E-04 |
| R/C | rs191549948 |
-1.456 | 1.0 | N | 0.795 | 0.538 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 0 | 8.6E-03 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/C | rs191549948 |
-1.456 | 1.0 | N | 0.795 | 0.538 | None | gnomAD-4.0.0 | 9.08135E-05 | None | None | None | None | N | None | 0 | 8.47549E-04 | None | 8.60462E-04 | 0 | None | 0 | 5.08992E-04 | 2.82698E-05 | 2.34269E-04 | 2.77796E-04 |
| R/H | rs775651612 |
-1.99 | 1.0 | D | 0.827 | 0.51 | None | gnomAD-2.1.1 | 6.21E-05 | None | None | None | None | N | None | 6.6E-05 | 1.6597E-04 | None | 0 | 0 | None | 0 | None | 0 | 6.7E-05 | 1.86428E-04 |
| R/H | rs775651612 |
-1.99 | 1.0 | D | 0.827 | 0.51 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs775651612 |
-1.99 | 1.0 | D | 0.827 | 0.51 | None | gnomAD-4.0.0 | 6.62807E-05 | None | None | None | None | N | None | 1.35722E-05 | 1.62719E-04 | None | 0 | 0 | None | 0 | 0 | 8.05691E-05 | 0 | 1.63516E-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 | 0.9658 | likely_pathogenic | 0.9611 | pathogenic | -1.928 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| R/C | 0.3929 | ambiguous | 0.464 | ambiguous | -1.821 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.519016641 | None | None | N |
| R/D | 0.9983 | likely_pathogenic | 0.9977 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| R/E | 0.9575 | likely_pathogenic | 0.9519 | pathogenic | -0.861 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/F | 0.9624 | likely_pathogenic | 0.9673 | pathogenic | -1.058 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/G | 0.9815 | likely_pathogenic | 0.9783 | pathogenic | -2.267 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.548223712 | None | None | N |
| R/H | 0.2834 | likely_benign | 0.3234 | benign | -2.138 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.525600006 | None | None | N |
| R/I | 0.9053 | likely_pathogenic | 0.8916 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/K | 0.493 | ambiguous | 0.4801 | ambiguous | -1.255 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| R/L | 0.8641 | likely_pathogenic | 0.8589 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.525600006 | None | None | N |
| R/M | 0.8976 | likely_pathogenic | 0.894 | pathogenic | -1.477 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/N | 0.9876 | likely_pathogenic | 0.9864 | pathogenic | -1.359 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -1.258 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.537374385 | None | None | N |
| R/Q | 0.3309 | likely_benign | 0.3252 | benign | -1.129 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/S | 0.9784 | likely_pathogenic | 0.9765 | pathogenic | -2.158 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | N | 0.505428155 | None | None | N |
| R/T | 0.9656 | likely_pathogenic | 0.953 | pathogenic | -1.727 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| R/V | 0.9151 | likely_pathogenic | 0.9056 | pathogenic | -1.258 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/W | 0.6628 | likely_pathogenic | 0.7179 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| R/Y | 0.894 | likely_pathogenic | 0.9149 | pathogenic | -0.518 | Destabilizing | 1.0 | D | 0.821 | 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.