Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 978 | 3157;3158;3159 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| N2AB | 978 | 3157;3158;3159 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| N2A | 978 | 3157;3158;3159 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| N2B | 932 | 3019;3020;3021 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| Novex-1 | 932 | 3019;3020;3021 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| Novex-2 | 932 | 3019;3020;3021 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
| Novex-3 | 978 | 3157;3158;3159 | chr2:178782974;178782973;178782972 | chr2:179647701;179647700;179647699 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 1.0 | D | 0.737 | 0.718 | 0.7040559 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-06 | 0 | 0 |
| R/T | None | None | 1.0 | D | 0.721 | 0.536 | 0.8334636 | gnomAD-4.0.0 | 1.36815E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7986E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9967 | likely_pathogenic | 0.9969 | pathogenic | -1.903 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| R/C | 0.9592 | likely_pathogenic | 0.9643 | pathogenic | -1.791 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| R/D | 0.9983 | likely_pathogenic | 0.9982 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| R/E | 0.9821 | likely_pathogenic | 0.9805 | pathogenic | -0.294 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| R/F | 0.9975 | likely_pathogenic | 0.9977 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/G | 0.9925 | likely_pathogenic | 0.9929 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.5922753 | None | None | N |
| R/H | 0.8504 | likely_pathogenic | 0.8573 | pathogenic | -2.113 | Highly Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/I | 0.9926 | likely_pathogenic | 0.9932 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| R/K | 0.7807 | likely_pathogenic | 0.7836 | pathogenic | -1.071 | Destabilizing | 0.997 | D | 0.523 | neutral | N | 0.40136072 | None | None | N |
| R/L | 0.9751 | likely_pathogenic | 0.9768 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/M | 0.9936 | likely_pathogenic | 0.994 | pathogenic | -1.257 | Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.6271562 | None | None | N |
| R/N | 0.9974 | likely_pathogenic | 0.9973 | pathogenic | -1.052 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/Q | 0.8313 | likely_pathogenic | 0.8363 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/S | 0.9963 | likely_pathogenic | 0.9963 | pathogenic | -2.125 | Highly Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.5985807 | None | None | N |
| R/T | 0.9963 | likely_pathogenic | 0.9964 | pathogenic | -1.676 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.58450663 | None | None | N |
| R/V | 0.994 | likely_pathogenic | 0.9945 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/W | 0.9366 | likely_pathogenic | 0.9423 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.65657973 | None | None | N |
| R/Y | 0.9886 | likely_pathogenic | 0.9893 | pathogenic | -0.674 | Destabilizing | 1.0 | D | 0.819 | 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.