Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3079 | 9460;9461;9462 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| N2AB | 3079 | 9460;9461;9462 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| N2A | 3079 | 9460;9461;9462 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| N2B | 3033 | 9322;9323;9324 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| Novex-1 | 3033 | 9322;9323;9324 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| Novex-2 | 3033 | 9322;9323;9324 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
| Novex-3 | 3079 | 9460;9461;9462 | chr2:178768084;178768083;178768082 | chr2:179632811;179632810;179632809 |
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 | rs141259583  |
-1.809 | 0.018 | D | 0.717 | 0.46 | None | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs141259583 |
-1.809 | 0.018 | D | 0.717 | 0.46 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/R | rs141259583 |
-1.809 | 0.018 | D | 0.717 | 0.46 | None | gnomAD-4.0.0 | 3.04475E-06 | None | None | None | None | N | None | 3.49479E-05 | 0 | None | 0 | 0 | None | 0 | 5.16529E-04 | 0 | 0 | 0 |
| C/Y | rs2154341551 |
None | 0.983 | D | 0.839 | 0.535 | 0.515036129008 | gnomAD-4.0.0 | 1.36816E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.8558 | likely_pathogenic | 0.8398 | pathogenic | -1.452 | Destabilizing | 0.587 | D | 0.663 | neutral | None | None | None | None | N |
| C/D | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -1.751 | Destabilizing | 0.961 | D | 0.86 | deleterious | None | None | None | None | N |
| C/E | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.492 | Destabilizing | 0.923 | D | 0.853 | deleterious | None | None | None | None | N |
| C/F | 0.9577 | likely_pathogenic | 0.9574 | pathogenic | -0.825 | Destabilizing | 0.983 | D | 0.833 | deleterious | N | 0.51773727 | None | None | N |
| C/G | 0.8299 | likely_pathogenic | 0.8126 | pathogenic | -1.806 | Destabilizing | 0.901 | D | 0.832 | deleterious | D | 0.538569735 | None | None | N |
| C/H | 0.999 | likely_pathogenic | 0.9989 | pathogenic | -2.04 | Highly Destabilizing | 0.989 | D | 0.858 | deleterious | None | None | None | None | N |
| C/I | 0.9214 | likely_pathogenic | 0.9035 | pathogenic | -0.485 | Destabilizing | 0.961 | D | 0.804 | deleterious | None | None | None | None | N |
| C/K | 0.9999 | likely_pathogenic | 0.9998 | pathogenic | -1.148 | Destabilizing | 0.633 | D | 0.827 | deleterious | None | None | None | None | N |
| C/L | 0.9454 | likely_pathogenic | 0.9404 | pathogenic | -0.485 | Destabilizing | 0.775 | D | 0.74 | deleterious | None | None | None | None | N |
| C/M | 0.959 | likely_pathogenic | 0.9587 | pathogenic | -0.108 | Destabilizing | 0.996 | D | 0.772 | deleterious | None | None | None | None | N |
| C/N | 0.9963 | likely_pathogenic | 0.9956 | pathogenic | -1.867 | Destabilizing | 0.923 | D | 0.859 | deleterious | None | None | None | None | N |
| C/P | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -0.787 | Destabilizing | 0.987 | D | 0.858 | deleterious | None | None | None | None | N |
| C/Q | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -1.316 | Destabilizing | 0.923 | D | 0.859 | deleterious | None | None | None | None | N |
| C/R | 0.9987 | likely_pathogenic | 0.9982 | pathogenic | -1.655 | Destabilizing | 0.018 | N | 0.717 | prob.delet. | D | 0.629527283 | None | None | N |
| C/S | 0.9263 | likely_pathogenic | 0.9137 | pathogenic | -2.1 | Highly Destabilizing | 0.722 | D | 0.773 | deleterious | D | 0.597221176 | None | None | N |
| C/T | 0.8762 | likely_pathogenic | 0.8827 | pathogenic | -1.666 | Destabilizing | 0.775 | D | 0.792 | deleterious | None | None | None | None | N |
| C/V | 0.7554 | likely_pathogenic | 0.7134 | pathogenic | -0.787 | Destabilizing | 0.875 | D | 0.788 | deleterious | None | None | None | None | N |
| C/W | 0.9968 | likely_pathogenic | 0.9963 | pathogenic | -1.338 | Destabilizing | 0.995 | D | 0.83 | deleterious | D | 0.629527283 | None | None | N |
| C/Y | 0.992 | likely_pathogenic | 0.9914 | pathogenic | -1.083 | Destabilizing | 0.983 | D | 0.839 | deleterious | D | 0.629527283 | 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.