Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2724 | 8395;8396;8397 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| N2AB | 2724 | 8395;8396;8397 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| N2A | 2724 | 8395;8396;8397 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| N2B | 2678 | 8257;8258;8259 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| Novex-1 | 2678 | 8257;8258;8259 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| Novex-2 | 2678 | 8257;8258;8259 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
| Novex-3 | 2724 | 8395;8396;8397 | chr2:178770622;178770621;178770620 | chr2:179635349;179635348;179635347 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1346689247  |
-1.258 | 1.0 | D | 0.679 | 0.706 | 0.721935125968 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| A/T | rs1346689247 |
-1.258 | 1.0 | D | 0.679 | 0.706 | 0.721935125968 | gnomAD-4.0.0 | 1.36825E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87547E-05 | 0 | 8.99297E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8323 | likely_pathogenic | 0.8649 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| A/D | 0.9921 | likely_pathogenic | 0.9954 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.718851237 | None | None | N |
| A/E | 0.9885 | likely_pathogenic | 0.9938 | pathogenic | -1.473 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| A/F | 0.9832 | likely_pathogenic | 0.9881 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| A/G | 0.3555 | ambiguous | 0.3419 | ambiguous | -1.371 | Destabilizing | 1.0 | D | 0.565 | neutral | D | 0.718775713 | None | None | N |
| A/H | 0.9956 | likely_pathogenic | 0.9974 | pathogenic | -1.7 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/I | 0.838 | likely_pathogenic | 0.9033 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| A/K | 0.9969 | likely_pathogenic | 0.9982 | pathogenic | -1.258 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| A/L | 0.8769 | likely_pathogenic | 0.9069 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| A/M | 0.8892 | likely_pathogenic | 0.9293 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| A/N | 0.9833 | likely_pathogenic | 0.9901 | pathogenic | -1.164 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| A/P | 0.9917 | likely_pathogenic | 0.9928 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.718775713 | None | None | N |
| A/Q | 0.9869 | likely_pathogenic | 0.9914 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| A/R | 0.9904 | likely_pathogenic | 0.9925 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/S | 0.3745 | ambiguous | 0.4416 | ambiguous | -1.583 | Destabilizing | 1.0 | D | 0.582 | neutral | D | 0.719038319 | None | None | N |
| A/T | 0.4649 | ambiguous | 0.5855 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | D | 0.681992377 | None | None | N |
| A/V | 0.4851 | ambiguous | 0.5987 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.602 | neutral | D | 0.548268019 | None | None | N |
| A/W | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.421 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| A/Y | 0.9939 | likely_pathogenic | 0.9962 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.88 | 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.