Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20772 | 62539;62540;62541 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| N2AB | 19131 | 57616;57617;57618 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| N2A | 18204 | 54835;54836;54837 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| N2B | 11707 | 35344;35345;35346 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| Novex-1 | 11832 | 35719;35720;35721 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| Novex-2 | 11899 | 35920;35921;35922 | chr2:178589411;178589410;178589409 | chr2:179454138;179454137;179454136 |
| 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 | rs878925775  |
-0.149 | 0.946 | N | 0.639 | 0.305 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| D/N | rs878925775 |
-0.149 | 0.946 | N | 0.639 | 0.305 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs878925775 |
-0.149 | 0.946 | N | 0.639 | 0.305 | None | gnomAD-4.0.0 | 4.33889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93399E-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 | 0.4367 | ambiguous | 0.6677 | pathogenic | -0.189 | Destabilizing | 0.716 | D | 0.607 | neutral | N | 0.500310637 | None | None | N |
| D/C | 0.876 | likely_pathogenic | 0.9585 | pathogenic | -0.094 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/E | 0.1685 | likely_benign | 0.4402 | ambiguous | -0.303 | Destabilizing | 0.016 | N | 0.159 | neutral | N | 0.485747873 | None | None | N |
| D/F | 0.829 | likely_pathogenic | 0.9047 | pathogenic | 0.131 | Stabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/G | 0.5569 | ambiguous | 0.7607 | pathogenic | -0.433 | Destabilizing | 0.834 | D | 0.623 | neutral | N | 0.49753916 | None | None | N |
| D/H | 0.5811 | likely_pathogenic | 0.7563 | pathogenic | 0.323 | Stabilizing | 0.993 | D | 0.683 | prob.neutral | N | 0.490310685 | None | None | N |
| D/I | 0.6053 | likely_pathogenic | 0.8119 | pathogenic | 0.416 | Stabilizing | 0.979 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/K | 0.7175 | likely_pathogenic | 0.8875 | pathogenic | 0.356 | Stabilizing | 0.921 | D | 0.67 | neutral | None | None | None | None | N |
| D/L | 0.6178 | likely_pathogenic | 0.7965 | pathogenic | 0.416 | Stabilizing | 0.959 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/M | 0.8051 | likely_pathogenic | 0.928 | pathogenic | 0.416 | Stabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/N | 0.2685 | likely_benign | 0.4547 | ambiguous | -0.158 | Destabilizing | 0.946 | D | 0.639 | neutral | N | 0.477433442 | None | None | N |
| D/P | 0.9482 | likely_pathogenic | 0.9681 | pathogenic | 0.238 | Stabilizing | 0.979 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/Q | 0.517 | ambiguous | 0.7608 | pathogenic | -0.073 | Destabilizing | 0.921 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/R | 0.7393 | likely_pathogenic | 0.8644 | pathogenic | 0.602 | Stabilizing | 0.959 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/S | 0.3346 | likely_benign | 0.5461 | ambiguous | -0.256 | Destabilizing | 0.769 | D | 0.569 | neutral | None | None | None | None | N |
| D/T | 0.4677 | ambiguous | 0.7138 | pathogenic | -0.05 | Destabilizing | 0.959 | D | 0.668 | neutral | None | None | None | None | N |
| D/V | 0.4007 | ambiguous | 0.6332 | pathogenic | 0.238 | Stabilizing | 0.946 | D | 0.715 | prob.delet. | N | 0.495083624 | None | None | N |
| D/W | 0.9526 | likely_pathogenic | 0.9723 | pathogenic | 0.321 | Stabilizing | 0.998 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/Y | 0.5307 | ambiguous | 0.6841 | pathogenic | 0.396 | Stabilizing | 0.998 | D | 0.727 | prob.delet. | D | 0.525051164 | 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.