Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| N2AB | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| N2A | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| N2B | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| Novex-1 | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| Novex-2 | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
| Novex-3 | 95 | 508;509;510 | chr2:178802150;178802149;178802148 | chr2:179666877;179666876;179666875 |
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/F | rs774434865  |
-1.803 | 1.0 | D | 0.863 | 0.454 | 0.669665416366 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -1.267(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.79E-06 | 0 |
| L/F | rs774434865 |
-1.803 | 1.0 | D | 0.863 | 0.454 | 0.669665416366 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.267(TCAP) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs774434865 |
-1.803 | 1.0 | D | 0.863 | 0.454 | 0.669665416366 | gnomAD-4.0.0 | 2.56115E-06 | None | None | None | -1.267(TCAP) | N | None | 1.6909E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39172E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.96 | likely_pathogenic | 0.9514 | pathogenic | -2.425 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | -0.486(TCAP) | N |
| L/C | 0.9807 | likely_pathogenic | 0.9794 | pathogenic | -1.637 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | -1.177(TCAP) | N |
| L/D | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -2.618 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | -0.709(TCAP) | N |
| L/E | 0.9957 | likely_pathogenic | 0.995 | pathogenic | -2.316 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | -0.894(TCAP) | N |
| L/F | 0.7633 | likely_pathogenic | 0.7794 | pathogenic | -1.449 | Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.710785548 | None | -1.267(TCAP) | N |
| L/G | 0.9893 | likely_pathogenic | 0.9856 | pathogenic | -3.039 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | -0.338(TCAP) | N |
| L/H | 0.9935 | likely_pathogenic | 0.9923 | pathogenic | -2.643 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.802932365 | None | -0.423(TCAP) | N |
| L/I | 0.2929 | likely_benign | 0.2995 | benign | -0.616 | Destabilizing | 0.991 | D | 0.611 | neutral | D | 0.60435731 | None | -0.996(TCAP) | N |
| L/K | 0.9943 | likely_pathogenic | 0.9935 | pathogenic | -1.751 | Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | -1.138(TCAP) | N |
| L/M | 0.4567 | ambiguous | 0.4706 | ambiguous | -0.653 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | -1.314(TCAP) | N |
| L/N | 0.9954 | likely_pathogenic | 0.9942 | pathogenic | -2.317 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | -0.685(TCAP) | N |
| L/P | 0.9982 | likely_pathogenic | 0.998 | pathogenic | -1.204 | Destabilizing | 1.0 | D | 0.916 | deleterious | D | 0.802932365 | None | -0.816(TCAP) | N |
| L/Q | 0.988 | likely_pathogenic | 0.9852 | pathogenic | -2.002 | Highly Destabilizing | 1.0 | D | 0.927 | deleterious | None | None | None | -0.821(TCAP) | N |
| L/R | 0.9879 | likely_pathogenic | 0.9849 | pathogenic | -1.776 | Destabilizing | 1.0 | D | 0.923 | deleterious | D | 0.802932365 | None | -1.194(TCAP) | N |
| L/S | 0.9958 | likely_pathogenic | 0.9945 | pathogenic | -3.028 | Highly Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | -0.356(TCAP) | N |
| L/T | 0.978 | likely_pathogenic | 0.9717 | pathogenic | -2.552 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | -0.568(TCAP) | N |
| L/V | 0.3676 | ambiguous | 0.365 | ambiguous | -1.204 | Destabilizing | 0.993 | D | 0.606 | neutral | N | 0.479940846 | None | -0.816(TCAP) | N |
| L/W | 0.9793 | likely_pathogenic | 0.9814 | pathogenic | -1.841 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | -1.742(TCAP) | N |
| L/Y | 0.9777 | likely_pathogenic | 0.9782 | pathogenic | -1.524 | Destabilizing | 0.999 | D | 0.903 | deleterious | None | None | None | -1.321(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.