Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28707 | 86344;86345;86346 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| N2AB | 27066 | 81421;81422;81423 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| N2A | 26139 | 78640;78641;78642 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| N2B | 19642 | 59149;59150;59151 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| Novex-1 | 19767 | 59524;59525;59526 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| Novex-2 | 19834 | 59725;59726;59727 | chr2:178560013;178560012;178560011 | chr2:179424740;179424739;179424738 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/E | rs754207859  |
-0.463 | 0.684 | N | 0.338 | 0.239 | None | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.38E-05 | 1.66445E-04 |
| G/E | rs754207859 |
-0.463 | 0.684 | N | 0.338 | 0.239 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| G/E | rs754207859 |
-0.463 | 0.684 | N | 0.338 | 0.239 | None | gnomAD-4.0.0 | 4.89609E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.61129E-05 | 0 | 1.60118E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1313 | likely_benign | 0.146 | benign | -0.309 | Destabilizing | 0.028 | N | 0.153 | neutral | N | 0.436014921 | None | None | N |
| G/C | 0.2063 | likely_benign | 0.2096 | benign | -0.522 | Destabilizing | 0.046 | N | 0.392 | neutral | None | None | None | None | N |
| G/D | 0.2602 | likely_benign | 0.2706 | benign | -0.49 | Destabilizing | 0.59 | D | 0.339 | neutral | None | None | None | None | N |
| G/E | 0.2673 | likely_benign | 0.2763 | benign | -0.492 | Destabilizing | 0.684 | D | 0.338 | neutral | N | 0.437783003 | None | None | N |
| G/F | 0.6046 | likely_pathogenic | 0.6327 | pathogenic | -0.601 | Destabilizing | 0.953 | D | 0.438 | neutral | None | None | None | None | N |
| G/H | 0.4585 | ambiguous | 0.461 | ambiguous | -0.731 | Destabilizing | 0.987 | D | 0.396 | neutral | None | None | None | None | N |
| G/I | 0.3175 | likely_benign | 0.3348 | benign | 0.115 | Stabilizing | 0.91 | D | 0.435 | neutral | None | None | None | None | N |
| G/K | 0.483 | ambiguous | 0.4846 | ambiguous | -0.676 | Destabilizing | 0.742 | D | 0.338 | neutral | None | None | None | None | N |
| G/L | 0.4258 | ambiguous | 0.4612 | ambiguous | 0.115 | Stabilizing | 0.59 | D | 0.391 | neutral | None | None | None | None | N |
| G/M | 0.4668 | ambiguous | 0.4831 | ambiguous | -0.154 | Destabilizing | 0.996 | D | 0.43 | neutral | None | None | None | None | N |
| G/N | 0.2524 | likely_benign | 0.2746 | benign | -0.552 | Destabilizing | 0.037 | N | 0.129 | neutral | None | None | None | None | N |
| G/P | 0.8794 | likely_pathogenic | 0.8753 | pathogenic | 0.014 | Stabilizing | 0.953 | D | 0.397 | neutral | None | None | None | None | N |
| G/Q | 0.3915 | ambiguous | 0.4028 | ambiguous | -0.598 | Destabilizing | 0.953 | D | 0.421 | neutral | None | None | None | None | N |
| G/R | 0.4197 | ambiguous | 0.4166 | ambiguous | -0.514 | Destabilizing | 0.939 | D | 0.379 | neutral | N | 0.450427013 | None | None | N |
| G/S | 0.1073 | likely_benign | 0.117 | benign | -0.832 | Destabilizing | 0.101 | N | 0.205 | neutral | None | None | None | None | N |
| G/T | 0.1595 | likely_benign | 0.1744 | benign | -0.728 | Destabilizing | 0.037 | N | 0.314 | neutral | None | None | None | None | N |
| G/V | 0.1991 | likely_benign | 0.212 | benign | 0.014 | Stabilizing | 0.684 | D | 0.39 | neutral | N | 0.454910113 | None | None | N |
| G/W | 0.5514 | ambiguous | 0.5476 | ambiguous | -1.024 | Destabilizing | 0.994 | D | 0.489 | neutral | N | 0.48139519 | None | None | N |
| G/Y | 0.4742 | ambiguous | 0.4594 | ambiguous | -0.501 | Destabilizing | 0.984 | D | 0.436 | 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.