Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2987 | 9184;9185;9186 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| N2AB | 2987 | 9184;9185;9186 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| N2A | 2987 | 9184;9185;9186 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| N2B | 2941 | 9046;9047;9048 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| Novex-1 | 2941 | 9046;9047;9048 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| Novex-2 | 2941 | 9046;9047;9048 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
| Novex-3 | 2987 | 9184;9185;9186 | chr2:178768877;178768876;178768875 | chr2:179633604;179633603;179633602 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.999 | N | 0.6 | 0.37 | 0.203808441222 | gnomAD-4.0.0 | 1.59072E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85654E-06 | 0 | 0 |
| T/I | rs1246906229  |
-0.134 | 1.0 | N | 0.775 | 0.55 | 0.385578977469 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1246906229 |
-0.134 | 1.0 | N | 0.775 | 0.55 | 0.385578977469 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92456E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1246906229 |
-0.134 | 1.0 | N | 0.775 | 0.55 | 0.385578977469 | gnomAD-4.0.0 | 3.04492E-06 | None | None | None | None | N | None | 1.74776E-05 | 0 | None | 0 | 1.13302E-04 | None | 0 | 0 | 1.20492E-06 | 0 | 0 |
| T/S | rs1294263680 |
-1.001 | 0.999 | N | 0.58 | 0.287 | 0.18274738541 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.62E-05 | 0 | 0 |
| T/S | rs1294263680 |
-1.001 | 0.999 | N | 0.58 | 0.287 | 0.18274738541 | gnomAD-4.0.0 | 4.77215E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88225E-05 | 0 | 5.71308E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2063 | likely_benign | 0.2217 | benign | -1.023 | Destabilizing | 0.999 | D | 0.6 | neutral | N | 0.506391957 | None | None | N |
| T/C | 0.6953 | likely_pathogenic | 0.7413 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| T/D | 0.8814 | likely_pathogenic | 0.9089 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| T/E | 0.8289 | likely_pathogenic | 0.8616 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| T/F | 0.6377 | likely_pathogenic | 0.7127 | pathogenic | -1.13 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| T/G | 0.6863 | likely_pathogenic | 0.7168 | pathogenic | -1.313 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| T/H | 0.568 | likely_pathogenic | 0.667 | pathogenic | -1.459 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| T/I | 0.3446 | ambiguous | 0.3887 | ambiguous | -0.328 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.456131302 | None | None | N |
| T/K | 0.6658 | likely_pathogenic | 0.7514 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| T/L | 0.2797 | likely_benign | 0.3056 | benign | -0.328 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| T/M | 0.1621 | likely_benign | 0.1782 | benign | -0.175 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| T/N | 0.3603 | ambiguous | 0.4109 | ambiguous | -0.65 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.506391957 | None | None | N |
| T/P | 0.7861 | likely_pathogenic | 0.8154 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.573146203 | None | None | N |
| T/Q | 0.5792 | likely_pathogenic | 0.6354 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| T/R | 0.5618 | ambiguous | 0.6488 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| T/S | 0.2348 | likely_benign | 0.2633 | benign | -1.022 | Destabilizing | 0.999 | D | 0.58 | neutral | N | 0.459325155 | None | None | N |
| T/V | 0.2779 | likely_benign | 0.2961 | benign | -0.528 | Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | N |
| T/W | 0.9099 | likely_pathogenic | 0.9375 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| T/Y | 0.6913 | likely_pathogenic | 0.7701 | pathogenic | -0.795 | Destabilizing | 1.0 | D | 0.787 | 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.