Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28253 | 84982;84983;84984 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| N2AB | 26612 | 80059;80060;80061 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| N2A | 25685 | 77278;77279;77280 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| N2B | 19188 | 57787;57788;57789 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| Novex-1 | 19313 | 58162;58163;58164 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| Novex-2 | 19380 | 58363;58364;58365 | chr2:178561375;178561374;178561373 | chr2:179426102;179426101;179426100 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 0.999 | N | 0.848 | 0.563 | 0.709402036203 | gnomAD-4.0.0 | 1.36841E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51915E-05 | None | 0 | 0 | 8.99467E-07 | 0 | 0 |
| C/Y | rs754491290  |
-0.996 | 0.999 | N | 0.852 | 0.449 | 0.534572409765 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| C/Y | rs754491290 |
-0.996 | 0.999 | N | 0.852 | 0.449 | 0.534572409765 | gnomAD-4.0.0 | 2.0526E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47794E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7387 | likely_pathogenic | 0.759 | pathogenic | -0.973 | Destabilizing | 0.995 | D | 0.503 | neutral | None | None | None | None | N |
| C/D | 0.9948 | likely_pathogenic | 0.9934 | pathogenic | -1.27 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| C/E | 0.9965 | likely_pathogenic | 0.9954 | pathogenic | -1.165 | Destabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| C/F | 0.8374 | likely_pathogenic | 0.7759 | pathogenic | -0.911 | Destabilizing | 0.999 | D | 0.853 | deleterious | N | 0.460854491 | None | None | N |
| C/G | 0.7403 | likely_pathogenic | 0.7302 | pathogenic | -1.228 | Destabilizing | 0.999 | D | 0.831 | deleterious | N | 0.483313612 | None | None | N |
| C/H | 0.9879 | likely_pathogenic | 0.9838 | pathogenic | -1.8 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| C/I | 0.5671 | likely_pathogenic | 0.5531 | ambiguous | -0.347 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| C/K | 0.9966 | likely_pathogenic | 0.9953 | pathogenic | -0.601 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| C/L | 0.7285 | likely_pathogenic | 0.7088 | pathogenic | -0.347 | Destabilizing | 0.998 | D | 0.602 | neutral | None | None | None | None | N |
| C/M | 0.8698 | likely_pathogenic | 0.8482 | pathogenic | 0.304 | Stabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| C/N | 0.9684 | likely_pathogenic | 0.9615 | pathogenic | -0.827 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| C/P | 0.8706 | likely_pathogenic | 0.8782 | pathogenic | -0.529 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| C/Q | 0.9872 | likely_pathogenic | 0.9837 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| C/R | 0.972 | likely_pathogenic | 0.9617 | pathogenic | -0.746 | Destabilizing | 0.999 | D | 0.848 | deleterious | N | 0.483313612 | None | None | N |
| C/S | 0.7721 | likely_pathogenic | 0.772 | pathogenic | -1.025 | Destabilizing | 0.999 | D | 0.763 | deleterious | N | 0.460347512 | None | None | N |
| C/T | 0.8193 | likely_pathogenic | 0.8183 | pathogenic | -0.771 | Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| C/V | 0.4428 | ambiguous | 0.4455 | ambiguous | -0.529 | Destabilizing | 0.998 | D | 0.655 | prob.neutral | None | None | None | None | N |
| C/W | 0.9745 | likely_pathogenic | 0.9622 | pathogenic | -1.23 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.483567102 | None | None | N |
| C/Y | 0.9468 | likely_pathogenic | 0.9225 | pathogenic | -0.926 | Destabilizing | 0.999 | D | 0.852 | deleterious | N | 0.460854491 | 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.