Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15279 | 46060;46061;46062 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| N2AB | 13638 | 41137;41138;41139 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| N2A | 12711 | 38356;38357;38358 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| N2B | 6214 | 18865;18866;18867 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| Novex-1 | 6339 | 19240;19241;19242 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| Novex-2 | 6406 | 19441;19442;19443 | chr2:178620775;178620774;178620773 | chr2:179485502;179485501;179485500 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | None | None | 0.437 | N | 0.48 | 0.166 | 0.380052290102 | gnomAD-4.0.0 | 6.84593E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15982E-05 | 0 |
| V/M | rs727504197  |
-0.43 | 0.968 | D | 0.701 | 0.273 | 0.509820907775 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-06 | 0 |
| V/M | rs727504197 |
-0.43 | 0.968 | D | 0.701 | 0.273 | 0.509820907775 | gnomAD-4.0.0 | 5.47674E-06 | None | None | None | None | N | None | 0 | 1.34264E-04 | None | 0 | 0 | None | 0 | 0 | 1.79983E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7467 | likely_pathogenic | 0.763 | pathogenic | -1.772 | Destabilizing | 0.026 | N | 0.43 | neutral | N | 0.456549324 | None | None | N |
| V/C | 0.9178 | likely_pathogenic | 0.9253 | pathogenic | -1.212 | Destabilizing | 0.997 | D | 0.775 | deleterious | None | None | None | None | N |
| V/D | 0.9954 | likely_pathogenic | 0.9957 | pathogenic | -2.261 | Highly Destabilizing | 0.988 | D | 0.857 | deleterious | None | None | None | None | N |
| V/E | 0.9908 | likely_pathogenic | 0.9911 | pathogenic | -2.029 | Highly Destabilizing | 0.968 | D | 0.813 | deleterious | D | 0.54173466 | None | None | N |
| V/F | 0.5002 | ambiguous | 0.5594 | ambiguous | -0.995 | Destabilizing | 0.976 | D | 0.789 | deleterious | None | None | None | None | N |
| V/G | 0.8997 | likely_pathogenic | 0.9048 | pathogenic | -2.319 | Highly Destabilizing | 0.811 | D | 0.827 | deleterious | D | 0.541551496 | None | None | N |
| V/H | 0.9958 | likely_pathogenic | 0.9964 | pathogenic | -2.147 | Highly Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| V/I | 0.0838 | likely_benign | 0.0934 | benign | -0.246 | Destabilizing | 0.015 | N | 0.313 | neutral | None | None | None | None | N |
| V/K | 0.9936 | likely_pathogenic | 0.9936 | pathogenic | -1.279 | Destabilizing | 0.976 | D | 0.819 | deleterious | None | None | None | None | N |
| V/L | 0.3661 | ambiguous | 0.4105 | ambiguous | -0.246 | Destabilizing | 0.437 | N | 0.48 | neutral | N | 0.441355638 | None | None | N |
| V/M | 0.3973 | ambiguous | 0.4528 | ambiguous | -0.338 | Destabilizing | 0.968 | D | 0.701 | prob.neutral | D | 0.540211183 | None | None | N |
| V/N | 0.9858 | likely_pathogenic | 0.9875 | pathogenic | -1.63 | Destabilizing | 0.988 | D | 0.856 | deleterious | None | None | None | None | N |
| V/P | 0.9949 | likely_pathogenic | 0.9958 | pathogenic | -0.728 | Destabilizing | 0.988 | D | 0.838 | deleterious | None | None | None | None | N |
| V/Q | 0.9892 | likely_pathogenic | 0.9897 | pathogenic | -1.437 | Destabilizing | 0.988 | D | 0.837 | deleterious | None | None | None | None | N |
| V/R | 0.9877 | likely_pathogenic | 0.9873 | pathogenic | -1.242 | Destabilizing | 0.988 | D | 0.856 | deleterious | None | None | None | None | N |
| V/S | 0.9509 | likely_pathogenic | 0.9552 | pathogenic | -2.253 | Highly Destabilizing | 0.851 | D | 0.808 | deleterious | None | None | None | None | N |
| V/T | 0.8656 | likely_pathogenic | 0.8795 | pathogenic | -1.874 | Destabilizing | 0.919 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/W | 0.9935 | likely_pathogenic | 0.995 | pathogenic | -1.549 | Destabilizing | 0.999 | D | 0.836 | deleterious | None | None | None | None | N |
| V/Y | 0.9658 | likely_pathogenic | 0.971 | pathogenic | -1.112 | Destabilizing | 0.996 | D | 0.774 | 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.