Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27849 | 83770;83771;83772 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| N2AB | 26208 | 78847;78848;78849 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| N2A | 25281 | 76066;76067;76068 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| N2B | 18784 | 56575;56576;56577 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| Novex-1 | 18909 | 56950;56951;56952 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| Novex-2 | 18976 | 57151;57152;57153 | chr2:178562587;178562586;178562585 | chr2:179427314;179427313;179427312 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | None | None | 1.0 | D | 0.703 | 0.822 | 0.501685917333 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| G/R | rs1704096127  |
None | 1.0 | D | 0.906 | 0.83 | 0.830013694033 | gnomAD-4.0.0 | 1.37108E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00278E-07 | 0 | 1.65937E-05 |
| G/V | None | None | 1.0 | D | 0.89 | 0.807 | 0.90823639256 |
Rees (2021)
| None |
MmD 
|
comp het with R21201* | None | None | I | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Protein unfolded; cannot be re-folded | None | None | None | None | None | None | None | None | None | None | None |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.855 | likely_pathogenic | 0.8999 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.552425037 | None | None | I |
| G/C | 0.9707 | likely_pathogenic | 0.9824 | pathogenic | -1.109 | Destabilizing | 1.0 | D | 0.833 | deleterious | D | 0.564795301 | None | None | I |
| G/D | 0.9967 | likely_pathogenic | 0.9977 | pathogenic | -0.884 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.552932016 | None | None | I |
| G/E | 0.9981 | likely_pathogenic | 0.9987 | pathogenic | -0.935 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | I |
| G/F | 0.9981 | likely_pathogenic | 0.9987 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
| G/H | 0.9982 | likely_pathogenic | 0.9988 | pathogenic | -1.12 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| G/I | 0.9973 | likely_pathogenic | 0.9982 | pathogenic | -0.35 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | I |
| G/K | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -0.945 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | I |
| G/L | 0.9959 | likely_pathogenic | 0.9971 | pathogenic | -0.35 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| G/M | 0.9979 | likely_pathogenic | 0.9986 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| G/N | 0.9954 | likely_pathogenic | 0.9968 | pathogenic | -0.718 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | I |
| G/P | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | I |
| G/Q | 0.9979 | likely_pathogenic | 0.9985 | pathogenic | -0.907 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | I |
| G/R | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -0.704 | Destabilizing | 1.0 | D | 0.906 | deleterious | D | 0.551918058 | None | None | I |
| G/S | 0.6091 | likely_pathogenic | 0.674 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.815 | deleterious | N | 0.518892594 | None | None | I |
| G/T | 0.9732 | likely_pathogenic | 0.9812 | pathogenic | -1.02 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | I |
| G/V | 0.9941 | likely_pathogenic | 0.9961 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.89 | deleterious | D | 0.564288322 | None | None | I |
| G/W | 0.9979 | likely_pathogenic | 0.9985 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | I |
| G/Y | 0.9981 | likely_pathogenic | 0.9987 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.861 | 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.