Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22245 | 66958;66959;66960 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| N2AB | 20604 | 62035;62036;62037 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| N2A | 19677 | 59254;59255;59256 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| N2B | 13180 | 39763;39764;39765 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| Novex-1 | 13305 | 40138;40139;40140 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| Novex-2 | 13372 | 40339;40340;40341 | chr2:178581535;178581534;178581533 | chr2:179446262;179446261;179446260 |
| 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/E | rs1306264861  |
-0.072 | 0.003 | N | 0.229 | 0.093 | 0.193865811164 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.7E-05 | 0 |
| D/E | rs1306264861 |
-0.072 | 0.003 | N | 0.229 | 0.093 | 0.193865811164 | gnomAD-4.0.0 | 4.81058E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.32269E-06 | 0 | 0 |
| D/N | None | None | 0.682 | N | 0.557 | 0.175 | 0.306053231325 | gnomAD-4.0.0 | 1.37255E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87991E-05 | 0 | 9.01838E-07 | 0 | 0 |
| D/V | rs757282339 |
0.467 | 0.938 | N | 0.713 | 0.378 | 0.450539155747 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| D/V | rs757282339 |
0.467 | 0.938 | N | 0.713 | 0.378 | 0.450539155747 | 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 |
| D/V | rs757282339 |
0.467 | 0.938 | N | 0.713 | 0.378 | 0.450539155747 | gnomAD-4.0.0 | 3.86496E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.2301E-06 | 0 | 0 |
| D/Y | None | None | 0.979 | N | 0.788 | 0.377 | 0.499727662827 | gnomAD-4.0.0 | 8.92157E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.08221E-05 | 0 | 1.66218E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1727 | likely_benign | 0.1876 | benign | -0.473 | Destabilizing | 0.682 | D | 0.649 | prob.neutral | N | 0.487809178 | None | None | I |
| D/C | 0.6038 | likely_pathogenic | 0.6242 | pathogenic | -0.295 | Destabilizing | 0.996 | D | 0.819 | deleterious | None | None | None | None | I |
| D/E | 0.1291 | likely_benign | 0.1326 | benign | -0.638 | Destabilizing | 0.003 | N | 0.229 | neutral | N | 0.404766507 | None | None | I |
| D/F | 0.5231 | ambiguous | 0.5191 | ambiguous | 0.063 | Stabilizing | 0.984 | D | 0.793 | deleterious | None | None | None | None | I |
| D/G | 0.3474 | ambiguous | 0.3754 | ambiguous | -0.823 | Destabilizing | 0.682 | D | 0.56 | neutral | N | 0.498218173 | None | None | I |
| D/H | 0.3397 | likely_benign | 0.3655 | ambiguous | -0.173 | Destabilizing | 0.938 | D | 0.649 | prob.neutral | N | 0.466783201 | None | None | I |
| D/I | 0.2493 | likely_benign | 0.2646 | benign | 0.451 | Stabilizing | 0.953 | D | 0.775 | deleterious | None | None | None | None | I |
| D/K | 0.455 | ambiguous | 0.485 | ambiguous | -0.395 | Destabilizing | 0.587 | D | 0.601 | neutral | None | None | None | None | I |
| D/L | 0.2686 | likely_benign | 0.2783 | benign | 0.451 | Stabilizing | 0.909 | D | 0.695 | prob.delet. | None | None | None | None | I |
| D/M | 0.4888 | ambiguous | 0.4974 | ambiguous | 0.726 | Stabilizing | 0.996 | D | 0.783 | deleterious | None | None | None | None | I |
| D/N | 0.1249 | likely_benign | 0.1274 | benign | -0.859 | Destabilizing | 0.682 | D | 0.557 | neutral | N | 0.497871456 | None | None | I |
| D/P | 0.5346 | ambiguous | 0.5545 | ambiguous | 0.168 | Stabilizing | 0.953 | D | 0.622 | neutral | None | None | None | None | I |
| D/Q | 0.3831 | ambiguous | 0.4035 | ambiguous | -0.713 | Destabilizing | 0.587 | D | 0.551 | neutral | None | None | None | None | I |
| D/R | 0.5253 | ambiguous | 0.5577 | ambiguous | -0.138 | Destabilizing | 0.02 | N | 0.541 | neutral | None | None | None | None | I |
| D/S | 0.1609 | likely_benign | 0.1691 | benign | -1.082 | Destabilizing | 0.74 | D | 0.547 | neutral | None | None | None | None | I |
| D/T | 0.2339 | likely_benign | 0.2463 | benign | -0.797 | Destabilizing | 0.74 | D | 0.578 | neutral | None | None | None | None | I |
| D/V | 0.149 | likely_benign | 0.1588 | benign | 0.168 | Stabilizing | 0.938 | D | 0.713 | prob.delet. | N | 0.515515854 | None | None | I |
| D/W | 0.8731 | likely_pathogenic | 0.8831 | pathogenic | 0.268 | Stabilizing | 0.996 | D | 0.823 | deleterious | None | None | None | None | I |
| D/Y | 0.2386 | likely_benign | 0.2528 | benign | 0.304 | Stabilizing | 0.979 | D | 0.788 | deleterious | N | 0.478646485 | 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.