Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27509 | 82750;82751;82752 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| N2AB | 25868 | 77827;77828;77829 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| N2A | 24941 | 75046;75047;75048 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| N2B | 18444 | 55555;55556;55557 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| Novex-1 | 18569 | 55930;55931;55932 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| Novex-2 | 18636 | 56131;56132;56133 | chr2:178563607;178563606;178563605 | chr2:179428334;179428333;179428332 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | rs1246168127  |
None | 1.0 | D | 0.887 | 0.476 | 0.564872276104 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93274E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs1246168127 |
None | 1.0 | D | 0.887 | 0.476 | 0.564872276104 | gnomAD-4.0.0 | 6.57601E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93274E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs1246168127 |
-1.083 | 1.0 | N | 0.687 | 0.42 | 0.358744678677 | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | N | None | 0 | 2.31723E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/Q | rs1246168127 |
-1.083 | 1.0 | N | 0.687 | 0.42 | 0.358744678677 | gnomAD-4.0.0 | 6.15789E-06 | None | None | None | None | N | None | 0 | 1.56523E-04 | None | 0 | 0 | None | 0 | 0 | 1.79897E-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 | 0.9625 | likely_pathogenic | 0.9631 | pathogenic | -2.073 | Highly Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| R/C | 0.5024 | ambiguous | 0.5325 | ambiguous | -1.896 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/D | 0.9947 | likely_pathogenic | 0.9947 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/E | 0.9453 | likely_pathogenic | 0.9493 | pathogenic | -0.715 | Destabilizing | 0.999 | D | 0.532 | neutral | None | None | None | None | N |
| R/F | 0.956 | likely_pathogenic | 0.9587 | pathogenic | -1.267 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| R/G | 0.926 | likely_pathogenic | 0.9345 | pathogenic | -2.432 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.51424002 | None | None | N |
| R/H | 0.2467 | likely_benign | 0.3003 | benign | -2.126 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/I | 0.9232 | likely_pathogenic | 0.9125 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/K | 0.248 | likely_benign | 0.2745 | benign | -1.218 | Destabilizing | 0.998 | D | 0.469 | neutral | None | None | None | None | N |
| R/L | 0.805 | likely_pathogenic | 0.8202 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.500806573 | None | None | N |
| R/M | 0.8783 | likely_pathogenic | 0.8813 | pathogenic | -1.493 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/N | 0.9757 | likely_pathogenic | 0.975 | pathogenic | -1.293 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/P | 0.998 | likely_pathogenic | 0.9978 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.532597764 | None | None | N |
| R/Q | 0.3526 | ambiguous | 0.3796 | ambiguous | -1.184 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.486510525 | None | None | N |
| R/S | 0.9814 | likely_pathogenic | 0.982 | pathogenic | -2.256 | Highly Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/T | 0.9586 | likely_pathogenic | 0.9572 | pathogenic | -1.805 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/V | 0.9423 | likely_pathogenic | 0.9371 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| R/W | 0.5916 | likely_pathogenic | 0.6435 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/Y | 0.8485 | likely_pathogenic | 0.8524 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.906 | 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.