Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21147 | 63664;63665;63666 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| N2AB | 19506 | 58741;58742;58743 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| N2A | 18579 | 55960;55961;55962 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| N2B | 12082 | 36469;36470;36471 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| Novex-1 | 12207 | 36844;36845;36846 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| Novex-2 | 12274 | 37045;37046;37047 | chr2:178587968;178587967;178587966 | chr2:179452695;179452694;179452693 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 1.0 | D | 0.609 | 0.656 | 0.48300943003 | gnomAD-4.0.0 | 1.37062E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80059E-06 | 0 | 0 |
| A/T | rs72646853  |
-1.8 | 1.0 | D | 0.777 | 0.662 | None | gnomAD-2.1.1 | 5.39335E-04 | None | None | None | None | N | None | 0 | 1.14528E-04 | None | 2.9406E-04 | 0 | None | 3.29989E-03 | None | 4.03E-05 | 2.61656E-04 | 1.14123E-03 |
| A/T | rs72646853 |
-1.8 | 1.0 | D | 0.777 | 0.662 | None | gnomAD-3.1.2 | 3.15698E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 3.53107E-04 | 4.54921E-03 | 0 |
| A/T | rs72646853 |
-1.8 | 1.0 | D | 0.777 | 0.662 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| A/T | rs72646853 |
-1.8 | 1.0 | D | 0.777 | 0.662 | None |
Taylor (2011)
| None |
ARVC 
|
comp het with M35859T | None | None | N | Genetic analysis of TTN in 38 ARVC families, incomplete penetrance | None | None | None | None | None | None | None | None | None | None | None |
| A/T | rs72646853 |
-1.8 | 1.0 | D | 0.777 | 0.662 | None | gnomAD-4.0.0 | 4.20144E-04 | None | None | None | None | N | None | 2.6688E-05 | 6.69546E-05 | None | 3.05147E-04 | 2.24669E-05 | None | 3.13224E-05 | 1.48957E-03 | 2.12097E-04 | 4.00934E-03 | 5.77238E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8152 | likely_pathogenic | 0.8045 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/D | 0.9975 | likely_pathogenic | 0.9975 | pathogenic | -2.923 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.570131807 | None | None | N |
| A/E | 0.9955 | likely_pathogenic | 0.9949 | pathogenic | -2.7 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/F | 0.9887 | likely_pathogenic | 0.9887 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| A/G | 0.4913 | ambiguous | 0.4953 | ambiguous | -2.277 | Highly Destabilizing | 1.0 | D | 0.619 | neutral | D | 0.538643331 | None | None | N |
| A/H | 0.996 | likely_pathogenic | 0.9959 | pathogenic | -2.115 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/I | 0.9721 | likely_pathogenic | 0.9688 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| A/K | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/L | 0.9045 | likely_pathogenic | 0.8935 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/M | 0.9668 | likely_pathogenic | 0.9657 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| A/N | 0.9927 | likely_pathogenic | 0.9927 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| A/P | 0.9366 | likely_pathogenic | 0.9224 | pathogenic | -1.072 | Destabilizing | 1.0 | D | 0.844 | deleterious | D | 0.540164268 | None | None | N |
| A/Q | 0.987 | likely_pathogenic | 0.9866 | pathogenic | -1.708 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| A/R | 0.9923 | likely_pathogenic | 0.992 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| A/S | 0.3044 | likely_benign | 0.3061 | benign | -2.317 | Highly Destabilizing | 1.0 | D | 0.609 | neutral | D | 0.52389321 | None | None | N |
| A/T | 0.8376 | likely_pathogenic | 0.8263 | pathogenic | -1.992 | Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.550760105 | None | None | N |
| A/V | 0.8866 | likely_pathogenic | 0.8728 | pathogenic | -1.072 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | D | 0.550506615 | None | None | N |
| A/W | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -1.359 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| A/Y | 0.9957 | likely_pathogenic | 0.996 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.877 | 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.