Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25947 | 78064;78065;78066 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| N2AB | 24306 | 73141;73142;73143 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| N2A | 23379 | 70360;70361;70362 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| N2B | 16882 | 50869;50870;50871 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| Novex-1 | 17007 | 51244;51245;51246 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| Novex-2 | 17074 | 51445;51446;51447 | chr2:178568293;178568292;178568291 | chr2:179433020;179433019;179433018 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs369737926  |
-0.153 | 0.892 | N | 0.571 | 0.332 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/G | rs369737926 |
-0.153 | 0.892 | N | 0.571 | 0.332 | None | gnomAD-4.0.0 | 3.60098E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.93752E-06 | 0 | 0 |
| R/S | rs1706725757 |
None | 0.892 | N | 0.657 | 0.3 | 0.321951552304 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs1706725757 |
None | 0.892 | N | 0.657 | 0.3 | 0.321951552304 | gnomAD-4.0.0 | 3.09903E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23858E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9768 | likely_pathogenic | 0.9796 | pathogenic | 0.03 | Stabilizing | 0.845 | D | 0.618 | neutral | None | None | None | None | N |
| R/C | 0.8144 | likely_pathogenic | 0.8272 | pathogenic | -0.221 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| R/D | 0.9894 | likely_pathogenic | 0.9902 | pathogenic | -0.234 | Destabilizing | 0.975 | D | 0.657 | neutral | None | None | None | None | N |
| R/E | 0.9586 | likely_pathogenic | 0.9651 | pathogenic | -0.191 | Destabilizing | 0.845 | D | 0.585 | neutral | None | None | None | None | N |
| R/F | 0.981 | likely_pathogenic | 0.9818 | pathogenic | -0.265 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| R/G | 0.9283 | likely_pathogenic | 0.9388 | pathogenic | -0.118 | Destabilizing | 0.892 | D | 0.571 | neutral | N | 0.520212385 | None | None | N |
| R/H | 0.6622 | likely_pathogenic | 0.6598 | pathogenic | -0.563 | Destabilizing | 0.987 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/I | 0.9696 | likely_pathogenic | 0.9736 | pathogenic | 0.375 | Stabilizing | 0.983 | D | 0.67 | neutral | N | 0.488814703 | None | None | N |
| R/K | 0.5563 | ambiguous | 0.5391 | ambiguous | -0.124 | Destabilizing | 0.025 | N | 0.293 | neutral | N | 0.46621377 | None | None | N |
| R/L | 0.9325 | likely_pathogenic | 0.94 | pathogenic | 0.375 | Stabilizing | 0.916 | D | 0.571 | neutral | None | None | None | None | N |
| R/M | 0.9581 | likely_pathogenic | 0.9649 | pathogenic | -0.045 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/N | 0.9832 | likely_pathogenic | 0.9834 | pathogenic | -0.004 | Destabilizing | 0.975 | D | 0.653 | neutral | None | None | None | None | N |
| R/P | 0.9944 | likely_pathogenic | 0.9947 | pathogenic | 0.278 | Stabilizing | 0.987 | D | 0.671 | neutral | None | None | None | None | N |
| R/Q | 0.6814 | likely_pathogenic | 0.7026 | pathogenic | -0.064 | Destabilizing | 0.975 | D | 0.647 | neutral | None | None | None | None | N |
| R/S | 0.9803 | likely_pathogenic | 0.9824 | pathogenic | -0.23 | Destabilizing | 0.892 | D | 0.657 | neutral | N | 0.488483969 | None | None | N |
| R/T | 0.9696 | likely_pathogenic | 0.9739 | pathogenic | -0.078 | Destabilizing | 0.967 | D | 0.673 | neutral | N | 0.50843238 | None | None | N |
| R/V | 0.9688 | likely_pathogenic | 0.9714 | pathogenic | 0.278 | Stabilizing | 0.975 | D | 0.675 | neutral | None | None | None | None | N |
| R/W | 0.8294 | likely_pathogenic | 0.8365 | pathogenic | -0.416 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/Y | 0.9428 | likely_pathogenic | 0.9417 | pathogenic | -0.01 | Destabilizing | 0.996 | D | 0.673 | 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.