Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21933 | 66022;66023;66024 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| N2AB | 20292 | 61099;61100;61101 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| N2A | 19365 | 58318;58319;58320 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| N2B | 12868 | 38827;38828;38829 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| Novex-1 | 12993 | 39202;39203;39204 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| Novex-2 | 13060 | 39403;39404;39405 | chr2:178583006;178583005;178583004 | chr2:179447733;179447732;179447731 |
| 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/H | rs1453626597  |
-0.876 | 0.97 | N | 0.725 | 0.398 | 0.280181792013 | gnomAD-4.0.0 | 1.62746E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.08128E-05 |
| D/N | rs1453626597 |
-0.766 | 0.822 | N | 0.56 | 0.313 | 0.241078983079 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 2.98E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1453626597 |
-0.766 | 0.822 | N | 0.56 | 0.313 | 0.241078983079 | gnomAD-4.0.0 | 1.62746E-06 | None | None | None | None | N | None | 0 | 2.33776E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.1454 | likely_benign | 0.1467 | benign | -0.621 | Destabilizing | 0.698 | D | 0.646 | neutral | N | 0.464447608 | None | None | N |
| D/C | 0.5044 | ambiguous | 0.4695 | ambiguous | -0.178 | Destabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | N |
| D/E | 0.1339 | likely_benign | 0.1246 | benign | -0.773 | Destabilizing | 0.006 | N | 0.177 | neutral | N | 0.429198884 | None | None | N |
| D/F | 0.4498 | ambiguous | 0.4226 | ambiguous | -0.531 | Destabilizing | 0.993 | D | 0.765 | deleterious | None | None | None | None | N |
| D/G | 0.2475 | likely_benign | 0.2428 | benign | -0.938 | Destabilizing | 0.822 | D | 0.58 | neutral | N | 0.509027891 | None | None | N |
| D/H | 0.2378 | likely_benign | 0.2264 | benign | -0.902 | Destabilizing | 0.97 | D | 0.725 | prob.delet. | N | 0.484246877 | None | None | N |
| D/I | 0.1928 | likely_benign | 0.1741 | benign | 0.205 | Stabilizing | 0.978 | D | 0.775 | deleterious | None | None | None | None | N |
| D/K | 0.3424 | ambiguous | 0.3426 | ambiguous | -0.324 | Destabilizing | 0.019 | N | 0.361 | neutral | None | None | None | None | N |
| D/L | 0.2636 | likely_benign | 0.2442 | benign | 0.205 | Stabilizing | 0.956 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/M | 0.4096 | ambiguous | 0.376 | ambiguous | 0.73 | Stabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| D/N | 0.0769 | likely_benign | 0.0781 | benign | -0.682 | Destabilizing | 0.822 | D | 0.56 | neutral | N | 0.421427549 | None | None | N |
| D/P | 0.7198 | likely_pathogenic | 0.72 | pathogenic | -0.046 | Destabilizing | 0.978 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/Q | 0.2793 | likely_benign | 0.2706 | benign | -0.583 | Destabilizing | 0.754 | D | 0.566 | neutral | None | None | None | None | N |
| D/R | 0.4068 | ambiguous | 0.4062 | ambiguous | -0.289 | Destabilizing | 0.915 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/S | 0.1097 | likely_benign | 0.1121 | benign | -0.921 | Destabilizing | 0.86 | D | 0.547 | neutral | None | None | None | None | N |
| D/T | 0.1515 | likely_benign | 0.1472 | benign | -0.659 | Destabilizing | 0.86 | D | 0.618 | neutral | None | None | None | None | N |
| D/V | 0.1292 | likely_benign | 0.1211 | benign | -0.046 | Destabilizing | 0.942 | D | 0.737 | prob.delet. | N | 0.408498325 | None | None | N |
| D/W | 0.8484 | likely_pathogenic | 0.8232 | pathogenic | -0.413 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/Y | 0.1988 | likely_benign | 0.1911 | benign | -0.3 | Destabilizing | 0.99 | D | 0.765 | deleterious | N | 0.484420235 | 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.