Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31427 | 94504;94505;94506 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| N2AB | 29786 | 89581;89582;89583 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| N2A | 28859 | 86800;86801;86802 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| N2B | 22362 | 67309;67310;67311 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| Novex-1 | 22487 | 67684;67685;67686 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| Novex-2 | 22554 | 67885;67886;67887 | chr2:178547246;178547245;178547244 | chr2:179411973;179411972;179411971 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs776226409  |
-0.713 | 0.993 | N | 0.382 | 0.291 | 0.31501682445 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/L | rs776226409 |
-0.713 | 0.993 | N | 0.382 | 0.291 | 0.31501682445 | gnomAD-4.0.0 | 4.10533E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39699E-06 | 0 | 0 |
| I/V | None | None | 0.993 | N | 0.343 | 0.246 | 0.470890129789 | gnomAD-4.0.0 | 6.84222E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.957 | likely_pathogenic | 0.9615 | pathogenic | -2.816 | Highly Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| I/C | 0.9457 | likely_pathogenic | 0.9487 | pathogenic | -1.538 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -3.356 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| I/E | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -3.048 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| I/F | 0.671 | likely_pathogenic | 0.7006 | pathogenic | -1.747 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.482382695 | None | None | N |
| I/G | 0.9961 | likely_pathogenic | 0.9967 | pathogenic | -3.367 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| I/H | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -3.078 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| I/K | 0.9977 | likely_pathogenic | 0.9981 | pathogenic | -2.105 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| I/L | 0.1424 | likely_benign | 0.1496 | benign | -1.133 | Destabilizing | 0.993 | D | 0.382 | neutral | N | 0.39946697 | None | None | N |
| I/M | 0.2932 | likely_benign | 0.3126 | benign | -1.188 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.479104239 | None | None | N |
| I/N | 0.9959 | likely_pathogenic | 0.9969 | pathogenic | -2.847 | Highly Destabilizing | 1.0 | D | 0.918 | deleterious | N | 0.506869733 | None | None | N |
| I/P | 0.9979 | likely_pathogenic | 0.9981 | pathogenic | -1.69 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| I/Q | 0.9968 | likely_pathogenic | 0.9974 | pathogenic | -2.47 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| I/R | 0.9962 | likely_pathogenic | 0.9969 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| I/S | 0.9893 | likely_pathogenic | 0.9913 | pathogenic | -3.242 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.506616243 | None | None | N |
| I/T | 0.9765 | likely_pathogenic | 0.9795 | pathogenic | -2.786 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.495259938 | None | None | N |
| I/V | 0.1061 | likely_benign | 0.1082 | benign | -1.69 | Destabilizing | 0.993 | D | 0.343 | neutral | N | 0.420522606 | None | None | N |
| I/W | 0.9955 | likely_pathogenic | 0.9964 | pathogenic | -2.042 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| I/Y | 0.9845 | likely_pathogenic | 0.9872 | pathogenic | -1.941 | Destabilizing | 1.0 | D | 0.799 | 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.