Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28946 | 87061;87062;87063 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| N2AB | 27305 | 82138;82139;82140 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| N2A | 26378 | 79357;79358;79359 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| N2B | 19881 | 59866;59867;59868 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| Novex-1 | 20006 | 60241;60242;60243 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| Novex-2 | 20073 | 60442;60443;60444 | chr2:178558623;178558622;178558621 | chr2:179423350;179423349;179423348 |
| 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 | rs748587720  |
-2.765 | 1.0 | D | 0.845 | 0.592 | 0.614776886339 | gnomAD-2.1.1 | 2.54E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.56E-05 | 0 |
| P/A | rs748587720 |
-2.765 | 1.0 | D | 0.845 | 0.592 | 0.614776886339 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/A | rs748587720 |
-2.765 | 1.0 | D | 0.845 | 0.592 | 0.614776886339 | gnomAD-4.0.0 | 1.17935E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.611E-05 | 0 | 0 |
| P/H | rs777096362 |
-2.58 | 1.0 | D | 0.907 | 0.635 | 0.736517613924 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.37E-05 | None | 0 | 0 | 0 |
| P/H | rs777096362 |
-2.58 | 1.0 | D | 0.907 | 0.635 | 0.736517613924 | gnomAD-4.0.0 | 3.1963E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.90596E-05 | 0 |
| P/R | None | None | 1.0 | D | 0.943 | 0.663 | 0.714357514992 | gnomAD-4.0.0 | 1.59814E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86162E-06 | 0 | 0 |
| P/S | rs748587720 |
-3.075 | 1.0 | D | 0.885 | 0.635 | 0.64681522666 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 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 | 0.6533 | likely_pathogenic | 0.676 | pathogenic | -2.546 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.524558909 | None | None | N |
| P/C | 0.9567 | likely_pathogenic | 0.95 | pathogenic | -2.114 | Highly Destabilizing | 1.0 | D | 0.924 | deleterious | None | None | None | None | N |
| P/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.15 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| P/E | 0.9973 | likely_pathogenic | 0.9975 | pathogenic | -2.878 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| P/F | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.938 | deleterious | None | None | None | None | N |
| P/G | 0.993 | likely_pathogenic | 0.9935 | pathogenic | -3.053 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| P/H | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -2.551 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.571162673 | None | None | N |
| P/I | 0.7123 | likely_pathogenic | 0.7072 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.939 | deleterious | None | None | None | None | N |
| P/K | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -1.741 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/L | 0.7685 | likely_pathogenic | 0.775 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.551283991 | None | None | N |
| P/M | 0.9529 | likely_pathogenic | 0.9563 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| P/N | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -2.287 | Highly Destabilizing | 1.0 | D | 0.943 | deleterious | None | None | None | None | N |
| P/Q | 0.9937 | likely_pathogenic | 0.9944 | pathogenic | -1.987 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| P/R | 0.9953 | likely_pathogenic | 0.9956 | pathogenic | -1.758 | Destabilizing | 1.0 | D | 0.943 | deleterious | D | 0.559299389 | None | None | N |
| P/S | 0.9746 | likely_pathogenic | 0.9764 | pathogenic | -2.776 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.552804929 | None | None | N |
| P/T | 0.8901 | likely_pathogenic | 0.892 | pathogenic | -2.373 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.558792409 | None | None | N |
| P/V | 0.4858 | ambiguous | 0.4803 | ambiguous | -1.545 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| P/W | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| P/Y | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.37 | Destabilizing | 1.0 | D | 0.941 | 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.