Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15321 | 46186;46187;46188 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| N2AB | 13680 | 41263;41264;41265 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| N2A | 12753 | 38482;38483;38484 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| N2B | 6256 | 18991;18992;18993 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| Novex-1 | 6381 | 19366;19367;19368 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| Novex-2 | 6448 | 19567;19568;19569 | chr2:178620560;178620559;178620558 | chr2:179485287;179485286;179485285 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | None | None | 1.0 | D | 0.807 | 0.764 | 0.696206915315 | gnomAD-4.0.0 | 4.11036E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.401E-06 | 0 | 0 |
| F/L | rs2058106190  |
None | 0.999 | N | 0.685 | 0.569 | 0.585140355757 | gnomAD-4.0.0 | 6.8506E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00166E-07 | 0 | 0 |
| F/S | rs1344016534 |
-2.71 | 1.0 | D | 0.903 | 0.859 | 0.880461734194 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 0 | 0 |
| F/S | rs1344016534 |
-2.71 | 1.0 | D | 0.903 | 0.859 | 0.880461734194 | gnomAD-4.0.0 | 1.37011E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53177E-05 | None | 0 | 0 | 9.00156E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.993 | likely_pathogenic | 0.986 | pathogenic | -2.305 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| F/C | 0.9722 | likely_pathogenic | 0.9494 | pathogenic | -1.392 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.724064001 | None | None | N |
| F/D | 0.9996 | likely_pathogenic | 0.999 | pathogenic | -3.27 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| F/E | 0.9995 | likely_pathogenic | 0.9988 | pathogenic | -3.01 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| F/G | 0.9975 | likely_pathogenic | 0.9946 | pathogenic | -2.782 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| F/H | 0.9948 | likely_pathogenic | 0.9887 | pathogenic | -2.094 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| F/I | 0.7968 | likely_pathogenic | 0.7294 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.645134442 | None | None | N |
| F/K | 0.9991 | likely_pathogenic | 0.9982 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| F/L | 0.9619 | likely_pathogenic | 0.951 | pathogenic | -0.73 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.49557215 | None | None | N |
| F/M | 0.8977 | likely_pathogenic | 0.8932 | pathogenic | -0.609 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| F/N | 0.9984 | likely_pathogenic | 0.9962 | pathogenic | -2.754 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| F/P | 0.9999 | likely_pathogenic | 0.9996 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| F/Q | 0.9985 | likely_pathogenic | 0.9974 | pathogenic | -2.457 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| F/R | 0.9975 | likely_pathogenic | 0.9949 | pathogenic | -2.094 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| F/S | 0.9959 | likely_pathogenic | 0.9894 | pathogenic | -3.155 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | D | 0.724064001 | None | None | N |
| F/T | 0.996 | likely_pathogenic | 0.9912 | pathogenic | -2.759 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| F/V | 0.8401 | likely_pathogenic | 0.7769 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.707751804 | None | None | N |
| F/W | 0.9438 | likely_pathogenic | 0.923 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| F/Y | 0.7181 | likely_pathogenic | 0.6273 | pathogenic | -0.629 | Destabilizing | 0.999 | D | 0.645 | neutral | D | 0.72400115 | 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.