Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24646 | 74161;74162;74163 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| N2AB | 23005 | 69238;69239;69240 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| N2A | 22078 | 66457;66458;66459 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| N2B | 15581 | 46966;46967;46968 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| Novex-1 | 15706 | 47341;47342;47343 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| Novex-2 | 15773 | 47542;47543;47544 | chr2:178572196;178572195;178572194 | chr2:179436923;179436922;179436921 |
| 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/C | rs1424678846  |
-1.104 | 1.0 | N | 0.746 | 0.546 | 0.453401982733 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 2.32153E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66058E-04 |
| S/C | rs1424678846 |
-1.104 | 1.0 | N | 0.746 | 0.546 | 0.453401982733 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 4.58776E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs1424678846 |
-1.104 | 1.0 | N | 0.746 | 0.546 | 0.453401982733 | gnomAD-4.0.0 | 2.43511E-05 | None | None | None | None | N | None | 0 | 3.05188E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.8456E-05 |
| S/N | rs370902028 |
-1.352 | 0.997 | N | 0.691 | 0.393 | None | gnomAD-2.1.1 | 7.17E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 1.45518E-03 | 0 | None | 3.27E-05 | None | 0 | 2.36E-05 | 0 |
| S/N | rs370902028 |
-1.352 | 0.997 | N | 0.691 | 0.393 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 5.76369E-04 | 0 | None | 0 | 0 | 2.94E-05 | 2.06868E-04 | 0 |
| S/N | rs370902028 |
-1.352 | 0.997 | N | 0.691 | 0.393 | None | gnomAD-4.0.0 | 5.20666E-05 | None | None | None | None | N | None | 1.33515E-05 | 1.66772E-05 | None | 9.46202E-04 | 0 | None | 0 | 0 | 4.06911E-05 | 3.29388E-05 | 4.80446E-05 |
| S/T | None | None | 0.981 | N | 0.588 | 0.395 | 0.341226946553 | gnomAD-4.0.0 | 6.84363E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-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 | 0.2971 | likely_benign | 0.2853 | benign | -0.611 | Destabilizing | 0.997 | D | 0.579 | neutral | None | None | None | None | N |
| S/C | 0.3167 | likely_benign | 0.33 | benign | -0.408 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.487350354 | None | None | N |
| S/D | 0.972 | likely_pathogenic | 0.9748 | pathogenic | -0.389 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/E | 0.9807 | likely_pathogenic | 0.9807 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/F | 0.9032 | likely_pathogenic | 0.8703 | pathogenic | -0.891 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| S/G | 0.5154 | ambiguous | 0.4787 | ambiguous | -0.829 | Destabilizing | 1.0 | D | 0.572 | neutral | N | 0.470324692 | None | None | N |
| S/H | 0.9315 | likely_pathogenic | 0.9235 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| S/I | 0.9334 | likely_pathogenic | 0.9123 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.505174666 | None | None | N |
| S/K | 0.9961 | likely_pathogenic | 0.9954 | pathogenic | -0.751 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/L | 0.6702 | likely_pathogenic | 0.6046 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| S/M | 0.7821 | likely_pathogenic | 0.7444 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| S/N | 0.809 | likely_pathogenic | 0.7922 | pathogenic | -0.627 | Destabilizing | 0.997 | D | 0.691 | prob.neutral | N | 0.497439211 | None | None | N |
| S/P | 0.9981 | likely_pathogenic | 0.9974 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| S/Q | 0.9593 | likely_pathogenic | 0.9558 | pathogenic | -0.855 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| S/R | 0.9929 | likely_pathogenic | 0.9915 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.773 | deleterious | N | 0.500184235 | None | None | N |
| S/T | 0.4089 | ambiguous | 0.3827 | ambiguous | -0.65 | Destabilizing | 0.981 | D | 0.588 | neutral | N | 0.485829416 | None | None | N |
| S/V | 0.8617 | likely_pathogenic | 0.8424 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| S/W | 0.953 | likely_pathogenic | 0.9369 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| S/Y | 0.897 | likely_pathogenic | 0.8673 | pathogenic | -0.608 | Destabilizing | 1.0 | D | 0.804 | deleterious | 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.