Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23457 | 70594;70595;70596 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| N2AB | 21816 | 65671;65672;65673 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| N2A | 20889 | 62890;62891;62892 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| N2B | 14392 | 43399;43400;43401 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| Novex-1 | 14517 | 43774;43775;43776 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| Novex-2 | 14584 | 43975;43976;43977 | chr2:178575763;178575762;178575761 | chr2:179440490;179440489;179440488 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 0.698 | N | 0.548 | 0.232 | 0.268211541103 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/V | rs535816123  |
0.436 | 0.919 | N | 0.722 | 0.451 | 0.468834750356 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 0 | 1.73893E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/V | rs535816123 |
0.436 | 0.919 | N | 0.722 | 0.451 | 0.468834750356 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs535816123 |
0.436 | 0.919 | N | 0.722 | 0.451 | 0.468834750356 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| D/V | rs535816123 |
0.436 | 0.919 | N | 0.722 | 0.451 | 0.468834750356 | gnomAD-4.0.0 | 1.53793E-05 | None | None | None | None | I | None | 0 | 1.69509E-04 | None | 0 | 0 | None | 0 | 0 | 4.78886E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3464 | ambiguous | 0.437 | ambiguous | -0.442 | Destabilizing | 0.722 | D | 0.638 | neutral | N | 0.503685495 | None | None | I |
| D/C | 0.8429 | likely_pathogenic | 0.8933 | pathogenic | -0.334 | Destabilizing | 0.994 | D | 0.798 | deleterious | None | None | None | None | I |
| D/E | 0.1466 | likely_benign | 0.1766 | benign | -0.775 | Destabilizing | 0.003 | N | 0.131 | neutral | N | 0.411023263 | None | None | I |
| D/F | 0.88 | likely_pathogenic | 0.9182 | pathogenic | 0.073 | Stabilizing | 0.998 | D | 0.777 | deleterious | None | None | None | None | I |
| D/G | 0.351 | ambiguous | 0.4482 | ambiguous | -0.821 | Destabilizing | 0.789 | D | 0.587 | neutral | N | 0.470002886 | None | None | I |
| D/H | 0.6018 | likely_pathogenic | 0.676 | pathogenic | -0.311 | Destabilizing | 0.98 | D | 0.725 | prob.delet. | N | 0.481359191 | None | None | I |
| D/I | 0.7221 | likely_pathogenic | 0.7762 | pathogenic | 0.568 | Stabilizing | 0.994 | D | 0.775 | deleterious | None | None | None | None | I |
| D/K | 0.672 | likely_pathogenic | 0.7535 | pathogenic | -0.683 | Destabilizing | 0.072 | N | 0.351 | neutral | None | None | None | None | I |
| D/L | 0.6662 | likely_pathogenic | 0.7454 | pathogenic | 0.568 | Stabilizing | 0.989 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/M | 0.792 | likely_pathogenic | 0.8419 | pathogenic | 0.955 | Stabilizing | 0.999 | D | 0.774 | deleterious | None | None | None | None | I |
| D/N | 0.1859 | likely_benign | 0.219 | benign | -1.095 | Destabilizing | 0.698 | D | 0.548 | neutral | N | 0.497239525 | None | None | I |
| D/P | 0.9748 | likely_pathogenic | 0.9825 | pathogenic | 0.257 | Stabilizing | 0.776 | D | 0.7 | prob.neutral | None | None | None | None | I |
| D/Q | 0.5031 | ambiguous | 0.5813 | pathogenic | -0.908 | Destabilizing | 0.902 | D | 0.549 | neutral | None | None | None | None | I |
| D/R | 0.7424 | likely_pathogenic | 0.8074 | pathogenic | -0.449 | Destabilizing | 0.977 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/S | 0.2366 | likely_benign | 0.2931 | benign | -1.373 | Destabilizing | 0.873 | D | 0.489 | neutral | None | None | None | None | I |
| D/T | 0.4652 | ambiguous | 0.5412 | ambiguous | -1.066 | Destabilizing | 0.754 | D | 0.655 | neutral | None | None | None | None | I |
| D/V | 0.5045 | ambiguous | 0.5804 | pathogenic | 0.257 | Stabilizing | 0.919 | D | 0.722 | prob.delet. | N | 0.518038872 | None | None | I |
| D/W | 0.9761 | likely_pathogenic | 0.9821 | pathogenic | 0.202 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| D/Y | 0.5632 | ambiguous | 0.6348 | pathogenic | 0.276 | Stabilizing | 0.998 | D | 0.777 | deleterious | N | 0.468939702 | None | None | I |
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.