Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1171 | 3736;3737;3738 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| N2AB | 1171 | 3736;3737;3738 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| N2A | 1171 | 3736;3737;3738 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| N2B | 1125 | 3598;3599;3600 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| Novex-1 | 1125 | 3598;3599;3600 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| Novex-2 | 1125 | 3598;3599;3600 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
| Novex-3 | 1171 | 3736;3737;3738 | chr2:178781133;178781132;178781131 | chr2:179645860;179645859;179645858 |
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 | rs773680642  |
-1.815 | 1.0 | D | 0.813 | 0.356 | 0.422524665647 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| L/F | rs773680642 |
-1.815 | 1.0 | D | 0.813 | 0.356 | 0.422524665647 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92234E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs773680642 |
-1.815 | 1.0 | D | 0.813 | 0.356 | 0.422524665647 | gnomAD-4.0.0 | 2.56165E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.42554E-05 | None | 0 | 0 | 2.39217E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9787 | likely_pathogenic | 0.9815 | pathogenic | -2.663 | Highly Destabilizing | 0.999 | D | 0.756 | deleterious | None | None | None | None | N |
| L/C | 0.9839 | likely_pathogenic | 0.9837 | pathogenic | -1.881 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.071 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/E | 0.9983 | likely_pathogenic | 0.9989 | pathogenic | -2.783 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/F | 0.9133 | likely_pathogenic | 0.9263 | pathogenic | -1.609 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.655324637 | None | None | N |
| L/G | 0.9969 | likely_pathogenic | 0.9976 | pathogenic | -3.266 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/H | 0.9965 | likely_pathogenic | 0.9977 | pathogenic | -2.855 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/I | 0.4071 | ambiguous | 0.3887 | ambiguous | -0.883 | Destabilizing | 0.999 | D | 0.59 | neutral | None | None | None | None | N |
| L/K | 0.9966 | likely_pathogenic | 0.9978 | pathogenic | -1.989 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| L/M | 0.6896 | likely_pathogenic | 0.692 | pathogenic | -0.906 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.644202794 | None | None | N |
| L/N | 0.9979 | likely_pathogenic | 0.9987 | pathogenic | -2.529 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| L/P | 0.9986 | likely_pathogenic | 0.9989 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/Q | 0.9948 | likely_pathogenic | 0.9968 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/R | 0.992 | likely_pathogenic | 0.9946 | pathogenic | -1.894 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/S | 0.9976 | likely_pathogenic | 0.9984 | pathogenic | -3.212 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | D | 0.734055674 | None | None | N |
| L/T | 0.989 | likely_pathogenic | 0.9913 | pathogenic | -2.762 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| L/V | 0.4913 | ambiguous | 0.4767 | ambiguous | -1.462 | Destabilizing | 0.999 | D | 0.594 | neutral | N | 0.476817888 | None | None | N |
| L/W | 0.994 | likely_pathogenic | 0.9957 | pathogenic | -2.051 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.734055674 | None | None | N |
| L/Y | 0.9929 | likely_pathogenic | 0.9948 | pathogenic | -1.759 | Destabilizing | 1.0 | D | 0.864 | 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.