Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28949 | 87070;87071;87072 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| N2AB | 27308 | 82147;82148;82149 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| N2A | 26381 | 79366;79367;79368 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| N2B | 19884 | 59875;59876;59877 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| Novex-1 | 20009 | 60250;60251;60252 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| Novex-2 | 20076 | 60451;60452;60453 | chr2:178558614;178558613;178558612 | chr2:179423341;179423340;179423339 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | None | None | 0.997 | D | 0.899 | 0.556 | 0.837659467078 | gnomAD-4.0.0 | 6.84979E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99692E-07 | 0 | 0 |
| L/P | rs745542033  |
None | 0.998 | N | 0.898 | 0.504 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/P | rs745542033 |
None | 0.998 | N | 0.898 | 0.504 | None | gnomAD-4.0.0 | 4.3422E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08681E-06 | 0 | 1.602E-05 |
| L/R | rs745542033 |
None | 0.994 | D | 0.847 | 0.574 | 0.823584059959 | gnomAD-4.0.0 | 6.84979E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99692E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6934 | likely_pathogenic | 0.7198 | pathogenic | -2.361 | Highly Destabilizing | 0.968 | D | 0.738 | prob.delet. | None | None | None | None | N |
| L/C | 0.8412 | likely_pathogenic | 0.8486 | pathogenic | -1.662 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/D | 0.9976 | likely_pathogenic | 0.9982 | pathogenic | -2.499 | Highly Destabilizing | 0.998 | D | 0.883 | deleterious | None | None | None | None | N |
| L/E | 0.9891 | likely_pathogenic | 0.9914 | pathogenic | -2.305 | Highly Destabilizing | 0.995 | D | 0.847 | deleterious | None | None | None | None | N |
| L/F | 0.5155 | ambiguous | 0.4653 | ambiguous | -1.377 | Destabilizing | 0.976 | D | 0.854 | deleterious | N | 0.498691249 | None | None | N |
| L/G | 0.9673 | likely_pathogenic | 0.9707 | pathogenic | -2.886 | Highly Destabilizing | 0.995 | D | 0.849 | deleterious | None | None | None | None | N |
| L/H | 0.9783 | likely_pathogenic | 0.9815 | pathogenic | -2.344 | Highly Destabilizing | 0.997 | D | 0.899 | deleterious | D | 0.541536031 | None | None | N |
| L/I | 0.1327 | likely_benign | 0.1414 | benign | -0.867 | Destabilizing | 0.958 | D | 0.684 | prob.neutral | N | 0.507715595 | None | None | N |
| L/K | 0.9881 | likely_pathogenic | 0.9906 | pathogenic | -1.789 | Destabilizing | 0.995 | D | 0.813 | deleterious | None | None | None | None | N |
| L/M | 0.2523 | likely_benign | 0.2597 | benign | -0.83 | Destabilizing | 0.998 | D | 0.823 | deleterious | None | None | None | None | N |
| L/N | 0.9859 | likely_pathogenic | 0.9889 | pathogenic | -2.015 | Highly Destabilizing | 0.995 | D | 0.885 | deleterious | None | None | None | None | N |
| L/P | 0.9064 | likely_pathogenic | 0.9069 | pathogenic | -1.343 | Destabilizing | 0.998 | D | 0.898 | deleterious | N | 0.48974591 | None | None | N |
| L/Q | 0.9676 | likely_pathogenic | 0.9749 | pathogenic | -1.92 | Destabilizing | 0.995 | D | 0.873 | deleterious | None | None | None | None | N |
| L/R | 0.9742 | likely_pathogenic | 0.9788 | pathogenic | -1.492 | Destabilizing | 0.994 | D | 0.847 | deleterious | D | 0.530179725 | None | None | N |
| L/S | 0.9606 | likely_pathogenic | 0.9669 | pathogenic | -2.717 | Highly Destabilizing | 0.995 | D | 0.815 | deleterious | None | None | None | None | N |
| L/T | 0.6789 | likely_pathogenic | 0.7355 | pathogenic | -2.381 | Highly Destabilizing | 0.995 | D | 0.801 | deleterious | None | None | None | None | N |
| L/V | 0.1373 | likely_benign | 0.1469 | benign | -1.343 | Destabilizing | 0.958 | D | 0.697 | prob.neutral | N | 0.484950592 | None | None | N |
| L/W | 0.9109 | likely_pathogenic | 0.9048 | pathogenic | -1.748 | Destabilizing | 0.999 | D | 0.872 | deleterious | None | None | None | None | N |
| L/Y | 0.9386 | likely_pathogenic | 0.9328 | pathogenic | -1.447 | Destabilizing | 0.18 | N | 0.561 | 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.