Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| N2AB | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| N2A | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| N2B | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| Novex-1 | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| Novex-2 | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
| Novex-3 | 89 | 490;491;492 | chr2:178802168;178802167;178802166 | chr2:179666895;179666894;179666893 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs200165636  |
-1.151 | 1.0 | D | 0.625 | 0.514 | None | gnomAD-2.1.1 | 1.37894E-04 | None | None | None | -0.196(TCAP) | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.7875E-04 | 1.38389E-04 |
| A/G | rs200165636 |
-1.151 | 1.0 | D | 0.625 | 0.514 | None | gnomAD-3.1.2 | 1.24862E-04 | None | None | None | -0.196(TCAP) | N | None | 1.44781E-04 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.61665E-04 | 0 | 4.77555E-04 |
| A/G | rs200165636 |
-1.151 | 1.0 | D | 0.625 | 0.514 | None | gnomAD-4.0.0 | 2.16237E-04 | None | None | None | -0.196(TCAP) | N | None | 1.06778E-04 | 1.6665E-05 | None | 0 | 0 | None | 0 | 0 | 2.82209E-04 | 0 | 1.12025E-04 |
| A/T | rs1259283214 |
None | 1.0 | N | 0.752 | 0.43 | 0.486135451721 | gnomAD-4.0.0 | 1.20039E-06 | None | None | None | -0.574(TCAP) | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs200165636 |
-0.061 | 1.0 | N | 0.707 | 0.393 | 0.619501705969 | gnomAD-2.1.1 | 7.95E-06 | None | None | None | -0.398(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| A/V | rs200165636 |
-0.061 | 1.0 | N | 0.707 | 0.393 | 0.619501705969 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | -0.398(TCAP) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/V | rs200165636 |
-0.061 | 1.0 | N | 0.707 | 0.393 | 0.619501705969 | gnomAD-4.0.0 | 8.05467E-06 | None | None | None | -0.398(TCAP) | N | None | 1.33472E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93232E-06 | 5.48968E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9262 | likely_pathogenic | 0.8963 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | -0.71(TCAP) | N |
| A/D | 0.5698 | likely_pathogenic | 0.5004 | ambiguous | -0.701 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | -1.349(TCAP) | N |
| A/E | 0.51 | ambiguous | 0.4712 | ambiguous | -0.747 | Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.574338801 | None | -1.456(TCAP) | N |
| A/F | 0.7029 | likely_pathogenic | 0.6415 | pathogenic | -0.937 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | 0.233(TCAP) | N |
| A/G | 0.3265 | likely_benign | 0.2773 | benign | -0.998 | Destabilizing | 1.0 | D | 0.625 | neutral | D | 0.655242522 | None | -0.196(TCAP) | N |
| A/H | 0.8323 | likely_pathogenic | 0.7968 | pathogenic | -1.102 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | -0.221(TCAP) | N |
| A/I | 0.4791 | ambiguous | 0.4135 | ambiguous | -0.301 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | -0.491(TCAP) | N |
| A/K | 0.7853 | likely_pathogenic | 0.7284 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | -1.557(TCAP) | N |
| A/L | 0.4529 | ambiguous | 0.4 | ambiguous | -0.301 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | -0.491(TCAP) | N |
| A/M | 0.4717 | ambiguous | 0.4186 | ambiguous | -0.317 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | -0.353(TCAP) | N |
| A/N | 0.5837 | likely_pathogenic | 0.5173 | ambiguous | -0.621 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | -0.499(TCAP) | N |
| A/P | 0.9601 | likely_pathogenic | 0.9659 | pathogenic | -0.415 | Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.722006704 | None | -0.398(TCAP) | N |
| A/Q | 0.5789 | likely_pathogenic | 0.549 | ambiguous | -0.79 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | -0.698(TCAP) | N |
| A/R | 0.7368 | likely_pathogenic | 0.6874 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | -1.538(TCAP) | N |
| A/S | 0.1466 | likely_benign | 0.1351 | benign | -1.012 | Destabilizing | 1.0 | D | 0.63 | neutral | N | 0.50787821 | None | -0.435(TCAP) | N |
| A/T | 0.1491 | likely_benign | 0.1285 | benign | -0.96 | Destabilizing | 1.0 | D | 0.752 | deleterious | N | 0.509106112 | None | -0.574(TCAP) | N |
| A/V | 0.2035 | likely_benign | 0.1746 | benign | -0.415 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.510387641 | None | -0.398(TCAP) | N |
| A/W | 0.9654 | likely_pathogenic | 0.9551 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | -0.109(TCAP) | N |
| A/Y | 0.8584 | likely_pathogenic | 0.8175 | pathogenic | -0.81 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | 0.28(TCAP) | 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.