Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28966 | 87121;87122;87123 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| N2AB | 27325 | 82198;82199;82200 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| N2A | 26398 | 79417;79418;79419 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| N2B | 19901 | 59926;59927;59928 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| Novex-1 | 20026 | 60301;60302;60303 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| Novex-2 | 20093 | 60502;60503;60504 | chr2:178558563;178558562;178558561 | chr2:179423290;179423289;179423288 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 1.0 | D | 0.825 | 0.692 | 0.622259118589 | gnomAD-4.0.0 | 1.59145E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8582E-06 | 0 | 0 |
| P/S | rs1216201291  |
-2.679 | 1.0 | D | 0.855 | 0.637 | 0.584086171949 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 1.16056E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1216201291 |
-2.679 | 1.0 | D | 0.855 | 0.637 | 0.584086171949 | gnomAD-4.0.0 | 6.3658E-06 | None | None | None | None | N | None | 0 | 9.14578E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8537 | likely_pathogenic | 0.8828 | pathogenic | -2.098 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.591347942 | None | None | N |
| P/C | 0.9914 | likely_pathogenic | 0.993 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| P/D | 0.9983 | likely_pathogenic | 0.9987 | pathogenic | -2.87 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| P/E | 0.9964 | likely_pathogenic | 0.9971 | pathogenic | -2.754 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| P/F | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.404 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| P/G | 0.9828 | likely_pathogenic | 0.9861 | pathogenic | -2.536 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/H | 0.9963 | likely_pathogenic | 0.9972 | pathogenic | -2.322 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | D | 0.640243602 | None | None | N |
| P/I | 0.9958 | likely_pathogenic | 0.9967 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| P/K | 0.9982 | likely_pathogenic | 0.9986 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| P/L | 0.9739 | likely_pathogenic | 0.9793 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.903 | deleterious | D | 0.613696469 | None | None | N |
| P/M | 0.9944 | likely_pathogenic | 0.996 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| P/N | 0.9974 | likely_pathogenic | 0.998 | pathogenic | -1.934 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/Q | 0.9942 | likely_pathogenic | 0.9959 | pathogenic | -1.946 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/R | 0.9948 | likely_pathogenic | 0.9959 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.614503687 | None | None | N |
| P/S | 0.9723 | likely_pathogenic | 0.9801 | pathogenic | -2.419 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.553565825 | None | None | N |
| P/T | 0.9645 | likely_pathogenic | 0.9756 | pathogenic | -2.195 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | D | 0.602461485 | None | None | N |
| P/V | 0.9822 | likely_pathogenic | 0.9856 | pathogenic | -1.277 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.907 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| P/Y | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -1.598 | Destabilizing | 1.0 | D | 0.897 | 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.