Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3209 | 9850;9851;9852 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| N2AB | 3209 | 9850;9851;9852 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| N2A | 3209 | 9850;9851;9852 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| N2B | 3163 | 9712;9713;9714 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| Novex-1 | 3163 | 9712;9713;9714 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| Novex-2 | 3163 | 9712;9713;9714 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
| Novex-3 | 3209 | 9850;9851;9852 | chr2:178766459;178766458;178766457 | chr2:179631186;179631185;179631184 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs1022645763  |
None | 0.999 | N | 0.455 | 0.145 | 0.0954503805726 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/D | rs1022645763 |
None | 0.999 | N | 0.455 | 0.145 | 0.0954503805726 | gnomAD-4.0.0 | 2.47827E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.38977E-06 | 0 | 0 |
| E/G | None | None | 1.0 | N | 0.677 | 0.461 | 0.250039746154 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3867 | ambiguous | 0.525 | ambiguous | -0.651 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.313621 | None | None | N |
| E/C | 0.9675 | likely_pathogenic | 0.9854 | pathogenic | -0.16 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/D | 0.1655 | likely_benign | 0.2234 | benign | -0.606 | Destabilizing | 0.999 | D | 0.455 | neutral | N | 0.340055134 | None | None | N |
| E/F | 0.9302 | likely_pathogenic | 0.9703 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/G | 0.4062 | ambiguous | 0.5714 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.326063213 | None | None | N |
| E/H | 0.7412 | likely_pathogenic | 0.8486 | pathogenic | -0.639 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| E/I | 0.8091 | likely_pathogenic | 0.9115 | pathogenic | 0.014 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| E/K | 0.3691 | ambiguous | 0.585 | pathogenic | -0.132 | Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.330878499 | None | None | N |
| E/L | 0.8144 | likely_pathogenic | 0.9084 | pathogenic | 0.014 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| E/M | 0.8082 | likely_pathogenic | 0.9027 | pathogenic | 0.349 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| E/N | 0.4288 | ambiguous | 0.5849 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| E/P | 0.9662 | likely_pathogenic | 0.9858 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| E/Q | 0.2935 | likely_benign | 0.3937 | ambiguous | -0.354 | Destabilizing | 1.0 | D | 0.619 | neutral | N | 0.349790958 | None | None | N |
| E/R | 0.5571 | ambiguous | 0.7307 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| E/S | 0.3956 | ambiguous | 0.5148 | ambiguous | -0.632 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | N |
| E/T | 0.5489 | ambiguous | 0.6939 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/V | 0.5975 | likely_pathogenic | 0.7605 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.387861411 | None | None | N |
| E/W | 0.9768 | likely_pathogenic | 0.9923 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8704 | likely_pathogenic | 0.9451 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | 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.