Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14415 | 43468;43469;43470 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| N2AB | 12774 | 38545;38546;38547 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| N2A | 11847 | 35764;35765;35766 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| N2B | 5350 | 16273;16274;16275 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| Novex-1 | 5475 | 16648;16649;16650 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| Novex-2 | 5542 | 16849;16850;16851 | chr2:178632763;178632762;178632761 | chr2:179497490;179497489;179497488 |
| 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/N | rs370342831  |
0.183 | 0.959 | N | 0.383 | 0.211 | None | gnomAD-2.1.1 | 5.38E-05 | None | None | None | None | N | None | 2.894E-04 | 2.83E-05 | None | 0 | 2.57308E-04 | None | 0 | None | 0 | 0 | 2.8177E-04 |
| S/N | rs370342831 |
0.183 | 0.959 | N | 0.383 | 0.211 | None | gnomAD-3.1.2 | 1.0523E-04 | None | None | None | None | N | None | 2.89659E-04 | 0 | 0 | 0 | 3.88048E-04 | None | 0 | 0 | 1.47E-05 | 0 | 4.78011E-04 |
| S/N | rs370342831 |
0.183 | 0.959 | N | 0.383 | 0.211 | None | gnomAD-4.0.0 | 2.85197E-05 | None | None | None | None | N | None | 1.60282E-04 | 1.66811E-05 | None | 0 | 1.11627E-04 | None | 0 | 0 | 1.69559E-06 | 0 | 4.16453E-04 |
| S/R | rs770940545 |
0.083 | 0.92 | N | 0.426 | 0.207 | 0.27855597813 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| S/R | rs770940545 |
0.083 | 0.92 | N | 0.426 | 0.207 | 0.27855597813 | gnomAD-4.0.0 | 1.59299E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86025E-06 | 0 | 0 |
| S/T | None | None | 0.134 | N | 0.131 | 0.187 | 0.235038932564 | gnomAD-4.0.0 | 6.84522E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15966E-05 | 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 | 0.09 | likely_benign | 0.0924 | benign | -0.634 | Destabilizing | 0.079 | N | 0.107 | neutral | None | None | None | None | N |
| S/C | 0.1873 | likely_benign | 0.1699 | benign | -0.424 | Destabilizing | 0.999 | D | 0.426 | neutral | D | 0.566565108 | None | None | N |
| S/D | 0.4737 | ambiguous | 0.552 | ambiguous | 0.646 | Stabilizing | 0.939 | D | 0.315 | neutral | None | None | None | None | N |
| S/E | 0.5354 | ambiguous | 0.6147 | pathogenic | 0.596 | Stabilizing | 0.884 | D | 0.34 | neutral | None | None | None | None | N |
| S/F | 0.2927 | likely_benign | 0.3215 | benign | -1.059 | Destabilizing | 0.997 | D | 0.516 | neutral | None | None | None | None | N |
| S/G | 0.1146 | likely_benign | 0.1089 | benign | -0.797 | Destabilizing | 0.704 | D | 0.333 | neutral | D | 0.564825835 | None | None | N |
| S/H | 0.4178 | ambiguous | 0.4342 | ambiguous | -1.186 | Destabilizing | 0.991 | D | 0.432 | neutral | None | None | None | None | N |
| S/I | 0.266 | likely_benign | 0.2971 | benign | -0.322 | Destabilizing | 0.976 | D | 0.475 | neutral | N | 0.513583285 | None | None | N |
| S/K | 0.6228 | likely_pathogenic | 0.6975 | pathogenic | -0.351 | Destabilizing | 0.884 | D | 0.32 | neutral | None | None | None | None | N |
| S/L | 0.1143 | likely_benign | 0.1267 | benign | -0.322 | Destabilizing | 0.939 | D | 0.431 | neutral | None | None | None | None | N |
| S/M | 0.2863 | likely_benign | 0.2906 | benign | -0.216 | Destabilizing | 0.997 | D | 0.438 | neutral | None | None | None | None | N |
| S/N | 0.1713 | likely_benign | 0.1837 | benign | -0.171 | Destabilizing | 0.959 | D | 0.383 | neutral | N | 0.500704535 | None | None | N |
| S/P | 0.4092 | ambiguous | 0.453 | ambiguous | -0.395 | Destabilizing | 0.991 | D | 0.438 | neutral | None | None | None | None | N |
| S/Q | 0.5335 | ambiguous | 0.567 | pathogenic | -0.325 | Destabilizing | 0.373 | N | 0.201 | neutral | None | None | None | None | N |
| S/R | 0.511 | ambiguous | 0.5793 | pathogenic | -0.257 | Destabilizing | 0.92 | D | 0.426 | neutral | N | 0.484932479 | None | None | N |
| S/T | 0.0993 | likely_benign | 0.105 | benign | -0.325 | Destabilizing | 0.134 | N | 0.131 | neutral | N | 0.496941844 | None | None | N |
| S/V | 0.2677 | likely_benign | 0.2843 | benign | -0.395 | Destabilizing | 0.939 | D | 0.427 | neutral | None | None | None | None | N |
| S/W | 0.4653 | ambiguous | 0.4819 | ambiguous | -1.009 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | N |
| S/Y | 0.2612 | likely_benign | 0.2842 | benign | -0.738 | Destabilizing | 0.997 | D | 0.516 | 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.