Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26902 | 80929;80930;80931 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| N2AB | 25261 | 76006;76007;76008 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| N2A | 24334 | 73225;73226;73227 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| N2B | 17837 | 53734;53735;53736 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| Novex-1 | 17962 | 54109;54110;54111 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| Novex-2 | 18029 | 54310;54311;54312 | chr2:178565428;178565427;178565426 | chr2:179430155;179430154;179430153 |
| 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/L | rs1287537055  |
-0.22 | 0.035 | N | 0.576 | 0.31 | 0.488827753106 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| P/L | rs1287537055 |
-0.22 | 0.035 | N | 0.576 | 0.31 | 0.488827753106 | 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 |
| P/L | rs1287537055 |
-0.22 | 0.035 | N | 0.576 | 0.31 | 0.488827753106 | gnomAD-4.0.0 | 2.56393E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78808E-06 | 0 | 0 |
| P/S | rs1024262797 |
-1.0 | 0.973 | N | 0.777 | 0.446 | 0.414539908741 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| P/S | rs1024262797 |
-1.0 | 0.973 | N | 0.777 | 0.446 | 0.414539908741 | 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 |
| P/S | rs1024262797 |
-1.0 | 0.973 | N | 0.777 | 0.446 | 0.414539908741 | gnomAD-4.0.0 | 1.17778E-05 | None | None | None | None | I | None | 1.33636E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2716E-05 | 0 | 4.80538E-05 |
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 | 0.1615 | likely_benign | 0.1655 | benign | -1.439 | Destabilizing | 0.834 | D | 0.617 | neutral | N | 0.488362128 | None | None | I |
| P/C | 0.7612 | likely_pathogenic | 0.7785 | pathogenic | -1.038 | Destabilizing | 0.998 | D | 0.793 | deleterious | None | None | None | None | I |
| P/D | 0.7379 | likely_pathogenic | 0.7508 | pathogenic | -1.203 | Destabilizing | 0.993 | D | 0.791 | deleterious | None | None | None | None | I |
| P/E | 0.573 | likely_pathogenic | 0.5827 | pathogenic | -1.217 | Destabilizing | 0.979 | D | 0.795 | deleterious | None | None | None | None | I |
| P/F | 0.7623 | likely_pathogenic | 0.7648 | pathogenic | -1.148 | Destabilizing | 0.978 | D | 0.797 | deleterious | None | None | None | None | I |
| P/G | 0.5553 | ambiguous | 0.5539 | ambiguous | -1.746 | Destabilizing | 0.979 | D | 0.755 | deleterious | None | None | None | None | I |
| P/H | 0.4079 | ambiguous | 0.4199 | ambiguous | -1.303 | Destabilizing | 0.998 | D | 0.785 | deleterious | None | None | None | None | I |
| P/I | 0.592 | likely_pathogenic | 0.5927 | pathogenic | -0.704 | Destabilizing | 0.921 | D | 0.76 | deleterious | None | None | None | None | I |
| P/K | 0.5979 | likely_pathogenic | 0.6288 | pathogenic | -1.235 | Destabilizing | 0.979 | D | 0.799 | deleterious | None | None | None | None | I |
| P/L | 0.2346 | likely_benign | 0.235 | benign | -0.704 | Destabilizing | 0.035 | N | 0.576 | neutral | N | 0.495808094 | None | None | I |
| P/M | 0.5424 | ambiguous | 0.5426 | ambiguous | -0.537 | Destabilizing | 0.978 | D | 0.799 | deleterious | None | None | None | None | I |
| P/N | 0.5958 | likely_pathogenic | 0.5894 | pathogenic | -0.998 | Destabilizing | 0.993 | D | 0.803 | deleterious | None | None | None | None | I |
| P/Q | 0.3547 | ambiguous | 0.3597 | ambiguous | -1.181 | Destabilizing | 0.991 | D | 0.818 | deleterious | N | 0.490639853 | None | None | I |
| P/R | 0.3885 | ambiguous | 0.4181 | ambiguous | -0.714 | Destabilizing | 0.973 | D | 0.803 | deleterious | D | 0.531189888 | None | None | I |
| P/S | 0.2583 | likely_benign | 0.2557 | benign | -1.527 | Destabilizing | 0.973 | D | 0.777 | deleterious | N | 0.487614886 | None | None | I |
| P/T | 0.215 | likely_benign | 0.2276 | benign | -1.43 | Destabilizing | 0.946 | D | 0.742 | deleterious | N | 0.488865426 | None | None | I |
| P/V | 0.4324 | ambiguous | 0.4382 | ambiguous | -0.913 | Destabilizing | 0.921 | D | 0.723 | prob.delet. | None | None | None | None | I |
| P/W | 0.8512 | likely_pathogenic | 0.8601 | pathogenic | -1.313 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | I |
| P/Y | 0.7526 | likely_pathogenic | 0.7668 | pathogenic | -1.033 | Destabilizing | 0.994 | D | 0.797 | 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.