Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1596 | 5011;5012;5013 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| N2AB | 1596 | 5011;5012;5013 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| N2A | 1596 | 5011;5012;5013 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| N2B | 1550 | 4873;4874;4875 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| Novex-1 | 1550 | 4873;4874;4875 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| Novex-2 | 1550 | 4873;4874;4875 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
| Novex-3 | 1596 | 5011;5012;5013 | chr2:178777177;178777176;178777175 | chr2:179641904;179641903;179641902 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 1.0 | D | 0.663 | 0.65 | 0.707775620182 | gnomAD-4.0.0 | 2.05229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69797E-06 | 0 | 0 |
| I/V | rs750570694  |
-1.039 | 0.993 | N | 0.381 | 0.303 | 0.730863594352 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.93E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs750570694 |
-1.039 | 0.993 | N | 0.381 | 0.303 | 0.730863594352 | gnomAD-4.0.0 | 6.84096E-07 | None | None | None | None | N | None | 0 | 0 | None | 3.82673E-05 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9454 | likely_pathogenic | 0.9044 | pathogenic | -2.447 | Highly Destabilizing | 0.999 | D | 0.482 | neutral | None | None | None | None | N |
| I/C | 0.9913 | likely_pathogenic | 0.984 | pathogenic | -1.519 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/D | 0.9998 | likely_pathogenic | 0.9995 | pathogenic | -3.397 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| I/E | 0.999 | likely_pathogenic | 0.9981 | pathogenic | -3.094 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/F | 0.8838 | likely_pathogenic | 0.8036 | pathogenic | -1.565 | Destabilizing | 1.0 | D | 0.663 | neutral | D | 0.590437127 | None | None | N |
| I/G | 0.9984 | likely_pathogenic | 0.9966 | pathogenic | -3.005 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/H | 0.9987 | likely_pathogenic | 0.9973 | pathogenic | -2.76 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/K | 0.9985 | likely_pathogenic | 0.997 | pathogenic | -2.108 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| I/L | 0.3891 | ambiguous | 0.3049 | benign | -0.773 | Destabilizing | 0.993 | D | 0.378 | neutral | N | 0.463180665 | None | None | N |
| I/M | 0.526 | ambiguous | 0.4134 | ambiguous | -0.742 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.554844724 | None | None | N |
| I/N | 0.9965 | likely_pathogenic | 0.993 | pathogenic | -2.839 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | D | 0.678001114 | None | None | N |
| I/P | 0.9967 | likely_pathogenic | 0.9943 | pathogenic | -1.322 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| I/Q | 0.9982 | likely_pathogenic | 0.9964 | pathogenic | -2.505 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| I/R | 0.9968 | likely_pathogenic | 0.9941 | pathogenic | -2.155 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| I/S | 0.9888 | likely_pathogenic | 0.9793 | pathogenic | -3.293 | Highly Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.715225437 | None | None | N |
| I/T | 0.9313 | likely_pathogenic | 0.8837 | pathogenic | -2.835 | Highly Destabilizing | 1.0 | D | 0.664 | neutral | D | 0.63318977 | None | None | N |
| I/V | 0.1652 | likely_benign | 0.1365 | benign | -1.322 | Destabilizing | 0.993 | D | 0.381 | neutral | N | 0.512541491 | None | None | N |
| I/W | 0.9982 | likely_pathogenic | 0.9963 | pathogenic | -2.005 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| I/Y | 0.9941 | likely_pathogenic | 0.9883 | pathogenic | -1.716 | Destabilizing | 1.0 | D | 0.753 | 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.