Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2888 | 8887;8888;8889 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| N2AB | 2888 | 8887;8888;8889 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| N2A | 2888 | 8887;8888;8889 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| N2B | 2842 | 8749;8750;8751 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| Novex-1 | 2842 | 8749;8750;8751 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| Novex-2 | 2842 | 8749;8750;8751 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
| Novex-3 | 2888 | 8887;8888;8889 | chr2:178769919;178769918;178769917 | chr2:179634646;179634645;179634644 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs1038686184  |
-0.919 | 0.005 | N | 0.116 | 0.261 | 0.523392987388 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/L | rs1038686184 |
-0.919 | 0.005 | N | 0.116 | 0.261 | 0.523392987388 | gnomAD-4.0.0 | 1.11341E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85659E-06 | 8.59623E-05 | 0 |
| M/V | rs1038686184 |
None | 0.704 | N | 0.413 | 0.322 | 0.542144099713 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs1038686184 |
None | 0.704 | N | 0.413 | 0.322 | 0.542144099713 | gnomAD-4.0.0 | 3.84187E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.42424E-05 | None | 0 | 0 | 4.78361E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8194 | likely_pathogenic | 0.8981 | pathogenic | -2.018 | Highly Destabilizing | 0.927 | D | 0.566 | neutral | None | None | None | None | N |
| M/C | 0.9282 | likely_pathogenic | 0.968 | pathogenic | -1.754 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| M/D | 0.9969 | likely_pathogenic | 0.9986 | pathogenic | -0.874 | Destabilizing | 0.997 | D | 0.726 | prob.delet. | None | None | None | None | N |
| M/E | 0.977 | likely_pathogenic | 0.9877 | pathogenic | -0.725 | Destabilizing | 0.997 | D | 0.695 | prob.neutral | None | None | None | None | N |
| M/F | 0.7861 | likely_pathogenic | 0.8495 | pathogenic | -0.608 | Destabilizing | 0.939 | D | 0.635 | neutral | None | None | None | None | N |
| M/G | 0.9622 | likely_pathogenic | 0.9829 | pathogenic | -2.457 | Highly Destabilizing | 0.997 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/H | 0.9856 | likely_pathogenic | 0.9941 | pathogenic | -1.674 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| M/I | 0.6945 | likely_pathogenic | 0.7985 | pathogenic | -0.807 | Destabilizing | 0.704 | D | 0.519 | neutral | N | 0.419640354 | None | None | N |
| M/K | 0.9046 | likely_pathogenic | 0.9557 | pathogenic | -0.905 | Destabilizing | 0.986 | D | 0.65 | neutral | N | 0.515559722 | None | None | N |
| M/L | 0.1908 | likely_benign | 0.2491 | benign | -0.807 | Destabilizing | 0.005 | N | 0.116 | neutral | N | 0.347658864 | None | None | N |
| M/N | 0.9804 | likely_pathogenic | 0.9898 | pathogenic | -1.025 | Destabilizing | 0.997 | D | 0.708 | prob.delet. | None | None | None | None | N |
| M/P | 0.8645 | likely_pathogenic | 0.9414 | pathogenic | -1.186 | Destabilizing | 0.997 | D | 0.704 | prob.neutral | None | None | None | None | N |
| M/Q | 0.8732 | likely_pathogenic | 0.9298 | pathogenic | -0.868 | Destabilizing | 0.997 | D | 0.663 | neutral | None | None | None | None | N |
| M/R | 0.9016 | likely_pathogenic | 0.958 | pathogenic | -0.75 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | D | 0.559473057 | None | None | N |
| M/S | 0.9452 | likely_pathogenic | 0.9705 | pathogenic | -1.732 | Destabilizing | 0.99 | D | 0.636 | neutral | None | None | None | None | N |
| M/T | 0.8385 | likely_pathogenic | 0.9193 | pathogenic | -1.449 | Destabilizing | 0.959 | D | 0.619 | neutral | D | 0.559062167 | None | None | N |
| M/V | 0.2043 | likely_benign | 0.2866 | benign | -1.186 | Destabilizing | 0.704 | D | 0.413 | neutral | N | 0.515428769 | None | None | N |
| M/W | 0.9774 | likely_pathogenic | 0.9898 | pathogenic | -0.705 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| M/Y | 0.9796 | likely_pathogenic | 0.9906 | pathogenic | -0.715 | Destabilizing | 0.997 | D | 0.716 | prob.delet. | 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.