Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2538 | 7837;7838;7839 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| N2AB | 2538 | 7837;7838;7839 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| N2A | 2538 | 7837;7838;7839 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| N2B | 2492 | 7699;7700;7701 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| Novex-1 | 2492 | 7699;7700;7701 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| Novex-2 | 2492 | 7699;7700;7701 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
| Novex-3 | 2538 | 7837;7838;7839 | chr2:178773352;178773351;178773350 | chr2:179638079;179638078;179638077 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs1274574174  |
-0.466 | 0.997 | N | 0.597 | 0.414 | 0.484037581386 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| G/D | rs1274574174 |
-0.466 | 0.997 | N | 0.597 | 0.414 | 0.484037581386 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.77555E-04 |
| G/D | rs1274574174 |
-0.466 | 0.997 | N | 0.597 | 0.414 | 0.484037581386 | gnomAD-4.0.0 | 9.29476E-06 | None | None | None | None | N | None | 1.33526E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01696E-05 | 0 | 3.20133E-05 |
| G/V | None | None | 0.997 | D | 0.751 | 0.428 | 0.681546189506 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79864E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1896 | likely_benign | 0.1804 | benign | -0.365 | Destabilizing | 0.989 | D | 0.473 | neutral | N | 0.505685218 | None | None | N |
| G/C | 0.3556 | ambiguous | 0.3411 | ambiguous | -0.78 | Destabilizing | 1.0 | D | 0.766 | deleterious | D | 0.549141635 | None | None | N |
| G/D | 0.2781 | likely_benign | 0.263 | benign | -0.411 | Destabilizing | 0.997 | D | 0.597 | neutral | N | 0.508993292 | None | None | N |
| G/E | 0.2671 | likely_benign | 0.2572 | benign | -0.503 | Destabilizing | 0.995 | D | 0.651 | neutral | None | None | None | None | N |
| G/F | 0.7744 | likely_pathogenic | 0.7721 | pathogenic | -0.783 | Destabilizing | 0.99 | D | 0.753 | deleterious | None | None | None | None | N |
| G/H | 0.5243 | ambiguous | 0.5067 | ambiguous | -0.925 | Destabilizing | 0.154 | N | 0.394 | neutral | None | None | None | None | N |
| G/I | 0.5794 | likely_pathogenic | 0.5546 | ambiguous | -0.144 | Destabilizing | 0.998 | D | 0.786 | deleterious | None | None | None | None | N |
| G/K | 0.5217 | ambiguous | 0.4926 | ambiguous | -0.923 | Destabilizing | 0.995 | D | 0.679 | prob.neutral | None | None | None | None | N |
| G/L | 0.6626 | likely_pathogenic | 0.6609 | pathogenic | -0.144 | Destabilizing | 0.995 | D | 0.705 | prob.neutral | None | None | None | None | N |
| G/M | 0.7179 | likely_pathogenic | 0.7137 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| G/N | 0.4006 | ambiguous | 0.3835 | ambiguous | -0.558 | Destabilizing | 0.995 | D | 0.521 | neutral | None | None | None | None | N |
| G/P | 0.4989 | ambiguous | 0.4505 | ambiguous | -0.177 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| G/Q | 0.4429 | ambiguous | 0.4259 | ambiguous | -0.728 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| G/R | 0.4695 | ambiguous | 0.4294 | ambiguous | -0.667 | Destabilizing | 0.994 | D | 0.723 | prob.delet. | N | 0.496507019 | None | None | N |
| G/S | 0.1481 | likely_benign | 0.1407 | benign | -0.816 | Destabilizing | 0.989 | D | 0.495 | neutral | N | 0.506836666 | None | None | N |
| G/T | 0.2925 | likely_benign | 0.2766 | benign | -0.819 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | N |
| G/V | 0.4202 | ambiguous | 0.3934 | ambiguous | -0.177 | Destabilizing | 0.997 | D | 0.751 | deleterious | D | 0.54474082 | None | None | N |
| G/W | 0.6378 | likely_pathogenic | 0.6193 | pathogenic | -1.097 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| G/Y | 0.5786 | likely_pathogenic | 0.5702 | pathogenic | -0.67 | Destabilizing | 0.643 | D | 0.435 | 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.