Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16884 | 50875;50876;50877 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| N2AB | 15243 | 45952;45953;45954 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| N2A | 14316 | 43171;43172;43173 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| N2B | 7819 | 23680;23681;23682 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| Novex-1 | 7944 | 24055;24056;24057 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| Novex-2 | 8011 | 24256;24257;24258 | chr2:178611579;178611578;178611577 | chr2:179476306;179476305;179476304 |
| 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/V | rs748958858  |
-1.519 | 0.993 | N | 0.381 | 0.24 | 0.567605623258 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.12095E-04 | None | 0 | None | 9.29E-05 | 0 | 0 |
| I/V | rs748958858 |
-1.519 | 0.993 | N | 0.381 | 0.24 | 0.567605623258 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs748958858 |
-1.519 | 0.993 | N | 0.381 | 0.24 | 0.567605623258 | gnomAD-4.0.0 | 1.15411E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.8676E-05 | None | 7.8456E-05 | 0 | 2.39557E-06 | 1.34037E-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 | 0.9782 | likely_pathogenic | 0.9865 | pathogenic | -2.233 | Highly Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | I |
| I/C | 0.9867 | likely_pathogenic | 0.9923 | pathogenic | -1.372 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| I/D | 0.9991 | likely_pathogenic | 0.9995 | pathogenic | -1.997 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
| I/E | 0.9966 | likely_pathogenic | 0.9983 | pathogenic | -1.9 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| I/F | 0.9261 | likely_pathogenic | 0.954 | pathogenic | -1.43 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.661871887 | None | None | I |
| I/G | 0.9979 | likely_pathogenic | 0.9988 | pathogenic | -2.665 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | I |
| I/H | 0.9978 | likely_pathogenic | 0.9988 | pathogenic | -1.912 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| I/K | 0.9954 | likely_pathogenic | 0.9974 | pathogenic | -1.681 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | I |
| I/L | 0.4761 | ambiguous | 0.5647 | pathogenic | -1.052 | Destabilizing | 0.993 | D | 0.401 | neutral | N | 0.507796327 | None | None | I |
| I/M | 0.5985 | likely_pathogenic | 0.6976 | pathogenic | -0.785 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.703965063 | None | None | I |
| I/N | 0.9835 | likely_pathogenic | 0.9907 | pathogenic | -1.654 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.706045759 | None | None | I |
| I/P | 0.9873 | likely_pathogenic | 0.9918 | pathogenic | -1.419 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| I/Q | 0.9953 | likely_pathogenic | 0.9976 | pathogenic | -1.726 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | I |
| I/R | 0.9935 | likely_pathogenic | 0.9964 | pathogenic | -1.126 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
| I/S | 0.986 | likely_pathogenic | 0.9916 | pathogenic | -2.331 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | D | 0.740976916 | None | None | I |
| I/T | 0.9564 | likely_pathogenic | 0.9753 | pathogenic | -2.109 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.682092324 | None | None | I |
| I/V | 0.0982 | likely_benign | 0.1033 | benign | -1.419 | Destabilizing | 0.993 | D | 0.381 | neutral | N | 0.483210971 | None | None | I |
| I/W | 0.9986 | likely_pathogenic | 0.9992 | pathogenic | -1.645 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| I/Y | 0.9931 | likely_pathogenic | 0.9959 | pathogenic | -1.412 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
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.