Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33415 | 100468;100469;100470 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| N2AB | 31774 | 95545;95546;95547 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| N2A | 30847 | 92764;92765;92766 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| N2B | 24350 | 73273;73274;73275 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| Novex-1 | 24475 | 73648;73649;73650 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| Novex-2 | 24542 | 73849;73850;73851 | chr2:178536504;178536503;178536502 | chr2:179401231;179401230;179401229 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.767 | N | 0.41 | 0.339 | 0.33440975612 | gnomAD-4.0.0 | 7.10326E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.20778E-07 | 0 | 0 |
| P/L | rs72648282  |
-0.651 | 0.999 | N | 0.823 | 0.521 | 0.564020812232 |
Taylor (2011)
| None |
ARVC 
|
het | None | None | N | Genetic analysis of TTN in 38 ARVC families; unknown penetrance | None | None | None | None | None | None | None | None | None | None | None |
| P/L | rs72648282 |
-0.651 | 0.999 | N | 0.823 | 0.521 | 0.564020812232 | gnomAD-4.0.0 | 3.47766E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.16717E-06 | 0 | 0 |
| P/S | None | None | 0.998 | N | 0.75 | 0.444 | 0.441221003447 | gnomAD-4.0.0 | 7.10326E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.20778E-07 | 0 | 0 |
| P/T | None | None | 0.999 | N | 0.771 | 0.486 | 0.487983534966 | gnomAD-4.0.0 | 7.10326E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.20778E-07 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0855 | likely_benign | 0.0824 | benign | -1.465 | Destabilizing | 0.767 | D | 0.41 | neutral | N | 0.474328167 | None | None | N |
| P/C | 0.6945 | likely_pathogenic | 0.6678 | pathogenic | -0.956 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| P/D | 0.7497 | likely_pathogenic | 0.8104 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| P/E | 0.3886 | ambiguous | 0.4504 | ambiguous | -1.384 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/F | 0.6803 | likely_pathogenic | 0.6925 | pathogenic | -1.038 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| P/G | 0.507 | ambiguous | 0.541 | ambiguous | -1.8 | Destabilizing | 0.997 | D | 0.752 | deleterious | None | None | None | None | N |
| P/H | 0.3489 | ambiguous | 0.3796 | ambiguous | -1.189 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| P/I | 0.3468 | ambiguous | 0.3426 | ambiguous | -0.624 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| P/K | 0.4089 | ambiguous | 0.507 | ambiguous | -1.259 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| P/L | 0.1585 | likely_benign | 0.1569 | benign | -0.624 | Destabilizing | 0.999 | D | 0.823 | deleterious | N | 0.494773547 | None | None | N |
| P/M | 0.3782 | ambiguous | 0.352 | ambiguous | -0.592 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| P/N | 0.5632 | ambiguous | 0.5836 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| P/Q | 0.2002 | likely_benign | 0.2108 | benign | -1.244 | Destabilizing | 1.0 | D | 0.863 | deleterious | N | 0.507635451 | None | None | N |
| P/R | 0.3166 | likely_benign | 0.4079 | ambiguous | -0.772 | Destabilizing | 0.999 | D | 0.871 | deleterious | N | 0.508096811 | None | None | N |
| P/S | 0.1982 | likely_benign | 0.2089 | benign | -1.633 | Destabilizing | 0.998 | D | 0.75 | deleterious | N | 0.516273577 | None | None | N |
| P/T | 0.1694 | likely_benign | 0.1761 | benign | -1.466 | Destabilizing | 0.999 | D | 0.771 | deleterious | N | 0.481517911 | None | None | N |
| P/V | 0.2564 | likely_benign | 0.2522 | benign | -0.872 | Destabilizing | 0.999 | D | 0.776 | deleterious | None | None | None | None | N |
| P/W | 0.8839 | likely_pathogenic | 0.9008 | pathogenic | -1.239 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/Y | 0.629 | likely_pathogenic | 0.6683 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.881 | 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.