Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27207 | 81844;81845;81846 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| N2AB | 25566 | 76921;76922;76923 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| N2A | 24639 | 74140;74141;74142 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| N2B | 18142 | 54649;54650;54651 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| Novex-1 | 18267 | 55024;55025;55026 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| Novex-2 | 18334 | 55225;55226;55227 | chr2:178564513;178564512;178564511 | chr2:179429240;179429239;179429238 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs755441250  |
-2.53 | 0.978 | D | 0.611 | 0.506 | 0.709532479457 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.2792E-04 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs755441250 |
-2.53 | 0.978 | D | 0.611 | 0.506 | 0.709532479457 | gnomAD-4.0.0 | 7.97123E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.39369E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1348567940 |
-0.255 | 0.37 | N | 0.259 | 0.219 | 0.391156786388 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| V/I | rs1348567940 |
-0.255 | 0.37 | N | 0.259 | 0.219 | 0.391156786388 | gnomAD-4.0.0 | 3.42381E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7998E-06 | 3.48254E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9143 | likely_pathogenic | 0.8676 | pathogenic | -2.179 | Highly Destabilizing | 0.978 | D | 0.611 | neutral | D | 0.547237705 | None | None | N |
| V/C | 0.9861 | likely_pathogenic | 0.9795 | pathogenic | -1.313 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| V/D | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -3.128 | Highly Destabilizing | 0.999 | D | 0.876 | deleterious | None | None | None | None | N |
| V/E | 0.9975 | likely_pathogenic | 0.9969 | pathogenic | -2.788 | Highly Destabilizing | 0.999 | D | 0.865 | deleterious | D | 0.559354479 | None | None | N |
| V/F | 0.9629 | likely_pathogenic | 0.9296 | pathogenic | -1.237 | Destabilizing | 0.998 | D | 0.801 | deleterious | None | None | None | None | N |
| V/G | 0.9855 | likely_pathogenic | 0.9797 | pathogenic | -2.797 | Highly Destabilizing | 0.999 | D | 0.883 | deleterious | D | 0.559354479 | None | None | N |
| V/H | 0.9994 | likely_pathogenic | 0.9991 | pathogenic | -2.784 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| V/I | 0.0923 | likely_benign | 0.0809 | benign | -0.364 | Destabilizing | 0.37 | N | 0.259 | neutral | N | 0.442410536 | None | None | N |
| V/K | 0.9977 | likely_pathogenic | 0.9974 | pathogenic | -1.703 | Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| V/L | 0.6757 | likely_pathogenic | 0.582 | pathogenic | -0.364 | Destabilizing | 0.9 | D | 0.49 | neutral | N | 0.508254313 | None | None | N |
| V/M | 0.8636 | likely_pathogenic | 0.7759 | pathogenic | -0.556 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/N | 0.9986 | likely_pathogenic | 0.9978 | pathogenic | -2.489 | Highly Destabilizing | 0.999 | D | 0.885 | deleterious | None | None | None | None | N |
| V/P | 0.9918 | likely_pathogenic | 0.9916 | pathogenic | -0.953 | Destabilizing | 0.999 | D | 0.874 | deleterious | None | None | None | None | N |
| V/Q | 0.9975 | likely_pathogenic | 0.9965 | pathogenic | -2.055 | Highly Destabilizing | 0.999 | D | 0.884 | deleterious | None | None | None | None | N |
| V/R | 0.9952 | likely_pathogenic | 0.9945 | pathogenic | -1.986 | Destabilizing | 0.999 | D | 0.888 | deleterious | None | None | None | None | N |
| V/S | 0.9897 | likely_pathogenic | 0.9835 | pathogenic | -2.922 | Highly Destabilizing | 0.999 | D | 0.868 | deleterious | None | None | None | None | N |
| V/T | 0.92 | likely_pathogenic | 0.885 | pathogenic | -2.414 | Highly Destabilizing | 0.992 | D | 0.673 | neutral | None | None | None | None | N |
| V/W | 0.9992 | likely_pathogenic | 0.9986 | pathogenic | -1.762 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.9979 | likely_pathogenic | 0.9965 | pathogenic | -1.446 | Destabilizing | 0.999 | D | 0.806 | 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.