Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20489 | 61690;61691;61692 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| N2AB | 18848 | 56767;56768;56769 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| N2A | 17921 | 53986;53987;53988 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| N2B | 11424 | 34495;34496;34497 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| Novex-1 | 11549 | 34870;34871;34872 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| Novex-2 | 11616 | 35071;35072;35073 | chr2:178590260;178590259;178590258 | chr2:179454987;179454986;179454985 |
| 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/K | rs562641765  |
0.008 | 0.997 | N | 0.553 | 0.4 | None | gnomAD-2.1.1 | 1.82E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.30203E-04 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs562641765 |
0.008 | 0.997 | N | 0.553 | 0.4 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.87898E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/K | rs562641765 |
0.008 | 0.997 | N | 0.553 | 0.4 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| R/K | rs562641765 |
0.008 | 0.997 | N | 0.553 | 0.4 | None | gnomAD-4.0.0 | 6.32606E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.57176E-04 | None | 0 | 0 | 2.57752E-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 | 0.8733 | likely_pathogenic | 0.8776 | pathogenic | -0.013 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | I |
| R/C | 0.5113 | ambiguous | 0.5456 | ambiguous | -0.207 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| R/D | 0.9679 | likely_pathogenic | 0.9659 | pathogenic | -0.059 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/E | 0.8518 | likely_pathogenic | 0.859 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/F | 0.8973 | likely_pathogenic | 0.9015 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| R/G | 0.8281 | likely_pathogenic | 0.8346 | pathogenic | -0.237 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.498645704 | None | None | I |
| R/H | 0.3018 | likely_benign | 0.3132 | benign | -0.716 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/I | 0.7628 | likely_pathogenic | 0.7826 | pathogenic | 0.549 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.485238711 | None | None | I |
| R/K | 0.2567 | likely_benign | 0.2808 | benign | -0.101 | Destabilizing | 0.997 | D | 0.553 | neutral | N | 0.492922288 | None | None | I |
| R/L | 0.6525 | likely_pathogenic | 0.6577 | pathogenic | 0.549 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| R/M | 0.7231 | likely_pathogenic | 0.7305 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| R/N | 0.9268 | likely_pathogenic | 0.9263 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| R/P | 0.8726 | likely_pathogenic | 0.8613 | pathogenic | 0.383 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/Q | 0.3282 | likely_benign | 0.3503 | ambiguous | 0.017 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| R/S | 0.9234 | likely_pathogenic | 0.9249 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.518722023 | None | None | I |
| R/T | 0.8057 | likely_pathogenic | 0.7988 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.513894993 | None | None | I |
| R/V | 0.7979 | likely_pathogenic | 0.8105 | pathogenic | 0.383 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/W | 0.4961 | ambiguous | 0.4815 | ambiguous | -0.159 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| R/Y | 0.7878 | likely_pathogenic | 0.7971 | pathogenic | 0.239 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | 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.