Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27534 | 82825;82826;82827 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| N2AB | 25893 | 77902;77903;77904 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| N2A | 24966 | 75121;75122;75123 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| N2B | 18469 | 55630;55631;55632 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| Novex-1 | 18594 | 56005;56006;56007 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| Novex-2 | 18661 | 56206;56207;56208 | chr2:178563532;178563531;178563530 | chr2:179428259;179428258;179428257 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1219137799  |
-2.386 | 1.0 | D | 0.869 | 0.772 | 0.895171775139 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/F | rs1219137799 |
-2.386 | 1.0 | D | 0.869 | 0.772 | 0.895171775139 | gnomAD-4.0.0 | 1.59129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| L/P | rs1704468647 |
None | 1.0 | D | 0.855 | 0.874 | 0.900478380912 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs1704468647 |
None | 1.0 | D | 0.855 | 0.874 | 0.900478380912 | gnomAD-4.0.0 | 6.57272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4705E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9712 | likely_pathogenic | 0.973 | pathogenic | -2.57 | Highly Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| L/C | 0.9534 | likely_pathogenic | 0.9546 | pathogenic | -2.09 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -2.516 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/E | 0.9966 | likely_pathogenic | 0.9976 | pathogenic | -2.42 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/F | 0.8606 | likely_pathogenic | 0.8606 | pathogenic | -1.896 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.663815418 | None | None | N |
| L/G | 0.9925 | likely_pathogenic | 0.9942 | pathogenic | -3.011 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/H | 0.9914 | likely_pathogenic | 0.9935 | pathogenic | -2.183 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | D | 0.680874161 | None | None | N |
| L/I | 0.4712 | ambiguous | 0.4256 | ambiguous | -1.354 | Destabilizing | 0.999 | D | 0.825 | deleterious | D | 0.641679414 | None | None | N |
| L/K | 0.9908 | likely_pathogenic | 0.9936 | pathogenic | -1.906 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/M | 0.5547 | ambiguous | 0.5645 | pathogenic | -1.174 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/N | 0.9923 | likely_pathogenic | 0.9948 | pathogenic | -1.977 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| L/P | 0.9946 | likely_pathogenic | 0.9955 | pathogenic | -1.735 | Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.680874161 | None | None | N |
| L/Q | 0.984 | likely_pathogenic | 0.9891 | pathogenic | -2.083 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/R | 0.9809 | likely_pathogenic | 0.9868 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.655336049 | None | None | N |
| L/S | 0.9953 | likely_pathogenic | 0.9965 | pathogenic | -2.708 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/T | 0.9787 | likely_pathogenic | 0.9819 | pathogenic | -2.473 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/V | 0.5393 | ambiguous | 0.4961 | ambiguous | -1.735 | Destabilizing | 0.999 | D | 0.829 | deleterious | D | 0.605108122 | None | None | N |
| L/W | 0.9867 | likely_pathogenic | 0.9887 | pathogenic | -2.05 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| L/Y | 0.9864 | likely_pathogenic | 0.988 | pathogenic | -1.837 | Destabilizing | 1.0 | D | 0.827 | 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.