Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31263 | 94012;94013;94014 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| N2AB | 29622 | 89089;89090;89091 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| N2A | 28695 | 86308;86309;86310 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| N2B | 22198 | 66817;66818;66819 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| Novex-1 | 22323 | 67192;67193;67194 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| Novex-2 | 22390 | 67393;67394;67395 | chr2:178547839;178547838;178547837 | chr2:179412566;179412565;179412564 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1482369519  |
-0.323 | 0.002 | D | 0.267 | 0.128 | 0.338834610459 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs1482369519 |
-0.323 | 0.002 | D | 0.267 | 0.128 | 0.338834610459 | gnomAD-4.0.0 | 4.77328E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77408E-05 | None | 0 | 0 | 5.71562E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.075 | likely_benign | 0.0751 | benign | -0.782 | Destabilizing | 0.025 | N | 0.266 | neutral | None | None | None | None | N |
| S/C | 0.0916 | likely_benign | 0.0842 | benign | -0.719 | Destabilizing | 0.002 | N | 0.267 | neutral | D | 0.535907848 | None | None | N |
| S/D | 0.3299 | likely_benign | 0.3041 | benign | -0.682 | Destabilizing | 0.124 | N | 0.268 | neutral | None | None | None | None | N |
| S/E | 0.4112 | ambiguous | 0.3725 | ambiguous | -0.7 | Destabilizing | 0.055 | N | 0.267 | neutral | None | None | None | None | N |
| S/F | 0.1487 | likely_benign | 0.1457 | benign | -1.219 | Destabilizing | 0.497 | N | 0.489 | neutral | None | None | None | None | N |
| S/G | 0.0971 | likely_benign | 0.0942 | benign | -0.971 | Destabilizing | 0.042 | N | 0.245 | neutral | D | 0.527576367 | None | None | N |
| S/H | 0.1975 | likely_benign | 0.1801 | benign | -1.554 | Destabilizing | 0.002 | N | 0.268 | neutral | None | None | None | None | N |
| S/I | 0.1186 | likely_benign | 0.1133 | benign | -0.384 | Destabilizing | 0.096 | N | 0.403 | neutral | N | 0.512492271 | None | None | N |
| S/K | 0.4056 | ambiguous | 0.3532 | ambiguous | -0.666 | Destabilizing | 0.001 | N | 0.171 | neutral | None | None | None | None | N |
| S/L | 0.0878 | likely_benign | 0.0866 | benign | -0.384 | Destabilizing | 0.001 | N | 0.251 | neutral | None | None | None | None | N |
| S/M | 0.1344 | likely_benign | 0.1343 | benign | -0.006 | Destabilizing | 0.497 | N | 0.43 | neutral | None | None | None | None | N |
| S/N | 0.0983 | likely_benign | 0.0927 | benign | -0.673 | Destabilizing | 0.001 | N | 0.197 | neutral | N | 0.485438956 | None | None | N |
| S/P | 0.8335 | likely_pathogenic | 0.8325 | pathogenic | -0.487 | Destabilizing | 0.364 | N | 0.455 | neutral | None | None | None | None | N |
| S/Q | 0.3103 | likely_benign | 0.2871 | benign | -0.955 | Destabilizing | 0.22 | N | 0.355 | neutral | None | None | None | None | N |
| S/R | 0.3217 | likely_benign | 0.2719 | benign | -0.52 | Destabilizing | 0.096 | N | 0.391 | neutral | N | 0.478531626 | None | None | N |
| S/T | 0.0651 | likely_benign | 0.0651 | benign | -0.685 | Destabilizing | 0.001 | N | 0.138 | neutral | N | 0.475435393 | None | None | N |
| S/V | 0.1318 | likely_benign | 0.1259 | benign | -0.487 | Destabilizing | 0.004 | N | 0.283 | neutral | None | None | None | None | N |
| S/W | 0.2567 | likely_benign | 0.2497 | benign | -1.175 | Destabilizing | 0.958 | D | 0.471 | neutral | None | None | None | None | N |
| S/Y | 0.1463 | likely_benign | 0.1375 | benign | -0.882 | Destabilizing | 0.331 | N | 0.493 | neutral | 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.