Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23926 | 72001;72002;72003 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| N2AB | 22285 | 67078;67079;67080 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| N2A | 21358 | 64297;64298;64299 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| N2B | 14861 | 44806;44807;44808 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| Novex-1 | 14986 | 45181;45182;45183 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| Novex-2 | 15053 | 45382;45383;45384 | chr2:178574356;178574355;178574354 | chr2:179439083;179439082;179439081 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/Y | rs755974144  |
0.344 | 1.0 | N | 0.836 | 0.593 | 0.535005106435 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/Y | rs755974144 |
0.344 | 1.0 | N | 0.836 | 0.593 | 0.535005106435 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs755974144 |
0.344 | 1.0 | N | 0.836 | 0.593 | 0.535005106435 | gnomAD-4.0.0 | 6.57523E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2806 | likely_benign | 0.2762 | benign | -0.598 | Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.488101962 | None | None | N |
| D/C | 0.8137 | likely_pathogenic | 0.8102 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/E | 0.4346 | ambiguous | 0.4056 | ambiguous | -0.799 | Destabilizing | 1.0 | D | 0.644 | neutral | N | 0.460135886 | None | None | N |
| D/F | 0.7517 | likely_pathogenic | 0.7586 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| D/G | 0.3529 | ambiguous | 0.3535 | ambiguous | -0.996 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.458855212 | None | None | N |
| D/H | 0.5934 | likely_pathogenic | 0.5599 | ambiguous | -0.761 | Destabilizing | 1.0 | D | 0.854 | deleterious | N | 0.520097418 | None | None | N |
| D/I | 0.7583 | likely_pathogenic | 0.7361 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| D/K | 0.8141 | likely_pathogenic | 0.7681 | pathogenic | -1.058 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| D/L | 0.6088 | likely_pathogenic | 0.5791 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| D/M | 0.8347 | likely_pathogenic | 0.8186 | pathogenic | 0.987 | Stabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| D/N | 0.2309 | likely_benign | 0.2207 | benign | -1.343 | Destabilizing | 1.0 | D | 0.799 | deleterious | N | 0.492838903 | None | None | N |
| D/P | 0.9573 | likely_pathogenic | 0.9583 | pathogenic | 0.143 | Stabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| D/Q | 0.6905 | likely_pathogenic | 0.6474 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| D/R | 0.8308 | likely_pathogenic | 0.7941 | pathogenic | -0.96 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| D/S | 0.1827 | likely_benign | 0.1804 | benign | -1.743 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| D/T | 0.5632 | ambiguous | 0.5471 | ambiguous | -1.414 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| D/V | 0.5892 | likely_pathogenic | 0.5704 | pathogenic | 0.143 | Stabilizing | 1.0 | D | 0.827 | deleterious | N | 0.500979205 | None | None | N |
| D/W | 0.9673 | likely_pathogenic | 0.9661 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| D/Y | 0.4113 | ambiguous | 0.4099 | ambiguous | -0.082 | Destabilizing | 1.0 | D | 0.836 | deleterious | N | 0.502246653 | 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.