Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15933 | 48022;48023;48024 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| N2AB | 14292 | 43099;43100;43101 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| N2A | 13365 | 40318;40319;40320 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| N2B | 6868 | 20827;20828;20829 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| Novex-1 | 6993 | 21202;21203;21204 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| Novex-2 | 7060 | 21403;21404;21405 | chr2:178617198;178617197;178617196 | chr2:179481925;179481924;179481923 |
| 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/G | rs2057499255  |
None | 0.994 | D | 0.572 | 0.488 | 0.455173453901 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs2057499255 |
None | 0.994 | D | 0.572 | 0.488 | 0.455173453901 | gnomAD-4.0.0 | 6.57999E-06 | None | None | None | None | N | None | 2.41324E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | None | None | 0.543 | D | 0.287 | 0.316 | 0.332646915603 | gnomAD-4.0.0 | 7.03322E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.15521E-07 | 0 | 0 |
| R/S | None | None | 0.989 | D | 0.529 | 0.425 | 0.345175991111 | gnomAD-4.0.0 | 1.40673E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.83114E-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 | 0.9451 | likely_pathogenic | 0.9495 | pathogenic | -1.935 | Destabilizing | 0.992 | D | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.5816 | likely_pathogenic | 0.5822 | pathogenic | -1.865 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/D | 0.9932 | likely_pathogenic | 0.994 | pathogenic | -0.941 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| R/E | 0.9179 | likely_pathogenic | 0.9263 | pathogenic | -0.725 | Destabilizing | 0.992 | D | 0.497 | neutral | None | None | None | None | N |
| R/F | 0.9693 | likely_pathogenic | 0.972 | pathogenic | -1.194 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/G | 0.9376 | likely_pathogenic | 0.9411 | pathogenic | -2.277 | Highly Destabilizing | 0.994 | D | 0.572 | neutral | D | 0.776156752 | None | None | N |
| R/H | 0.3895 | ambiguous | 0.3912 | ambiguous | -2.121 | Highly Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | N |
| R/I | 0.879 | likely_pathogenic | 0.8949 | pathogenic | -0.945 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | D | 0.64141921 | None | None | N |
| R/K | 0.3018 | likely_benign | 0.305 | benign | -1.23 | Destabilizing | 0.543 | D | 0.287 | neutral | D | 0.560893143 | None | None | N |
| R/L | 0.8396 | likely_pathogenic | 0.8477 | pathogenic | -0.945 | Destabilizing | 0.996 | D | 0.572 | neutral | None | None | None | None | N |
| R/M | 0.8857 | likely_pathogenic | 0.8885 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| R/N | 0.9695 | likely_pathogenic | 0.9711 | pathogenic | -1.227 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| R/P | 0.9981 | likely_pathogenic | 0.9987 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| R/Q | 0.2938 | likely_benign | 0.3035 | benign | -1.094 | Destabilizing | 0.998 | D | 0.507 | neutral | None | None | None | None | N |
| R/S | 0.9618 | likely_pathogenic | 0.9647 | pathogenic | -2.123 | Highly Destabilizing | 0.989 | D | 0.529 | neutral | D | 0.700606344 | None | None | N |
| R/T | 0.9071 | likely_pathogenic | 0.9204 | pathogenic | -1.694 | Destabilizing | 0.998 | D | 0.556 | neutral | D | 0.594666289 | None | None | N |
| R/V | 0.8984 | likely_pathogenic | 0.9154 | pathogenic | -1.264 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/W | 0.7584 | likely_pathogenic | 0.752 | pathogenic | -0.736 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/Y | 0.9197 | likely_pathogenic | 0.9199 | pathogenic | -0.57 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | 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.