Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20894 | 62905;62906;62907 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| N2AB | 19253 | 57982;57983;57984 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| N2A | 18326 | 55201;55202;55203 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| N2B | 11829 | 35710;35711;35712 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| Novex-1 | 11954 | 36085;36086;36087 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| Novex-2 | 12021 | 36286;36287;36288 | chr2:178589045;178589044;178589043 | chr2:179453772;179453771;179453770 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | rs370080086  |
-1.03 | 1.0 | N | 0.802 | 0.397 | None | gnomAD-2.1.1 | 9.06E-05 | None | None | None | None | I | None | 2.07159E-04 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 4.5E-05 | 1.41501E-04 | 0 |
| C/F | rs370080086 |
-1.03 | 1.0 | N | 0.802 | 0.397 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | I | None | 7.24E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 1.02959E-04 | 0 | 0 |
| C/F | rs370080086 |
-1.03 | 1.0 | N | 0.802 | 0.397 | None | gnomAD-4.0.0 | 1.45403E-04 | None | None | None | None | I | None | 5.33262E-05 | 3.33734E-05 | None | 0 | 0 | None | 0 | 3.3036E-04 | 1.84816E-04 | 0 | 1.28123E-04 |
| C/S | rs370080086 |
-0.528 | 1.0 | N | 0.735 | 0.469 | 0.58895048698 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 5.34E-05 | 0 | 0 |
| C/S | rs370080086 |
-0.528 | 1.0 | N | 0.735 | 0.469 | 0.58895048698 | gnomAD-4.0.0 | 6.86282E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.01873E-05 | 0 | 0 | 0 | 0 |
| C/Y | None | None | 1.0 | N | 0.808 | 0.392 | 0.693959955507 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | None | None | 1.0 | N | 0.808 | 0.392 | 0.693959955507 | gnomAD-4.0.0 | 6.57583E-06 | None | None | None | None | I | None | 2.41336E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.5788 | likely_pathogenic | 0.5717 | pathogenic | -1.234 | Destabilizing | 0.998 | D | 0.585 | neutral | None | None | None | None | I |
| C/D | 0.9304 | likely_pathogenic | 0.9226 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| C/E | 0.9608 | likely_pathogenic | 0.9554 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| C/F | 0.596 | likely_pathogenic | 0.5629 | ambiguous | -0.936 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.47249442 | None | None | I |
| C/G | 0.4054 | ambiguous | 0.4277 | ambiguous | -1.463 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.454923182 | None | None | I |
| C/H | 0.8765 | likely_pathogenic | 0.8698 | pathogenic | -1.562 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| C/I | 0.8208 | likely_pathogenic | 0.8069 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| C/K | 0.9805 | likely_pathogenic | 0.9791 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| C/L | 0.7674 | likely_pathogenic | 0.7672 | pathogenic | -0.688 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | I |
| C/M | 0.7596 | likely_pathogenic | 0.7361 | pathogenic | -0.043 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| C/N | 0.7433 | likely_pathogenic | 0.739 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | I |
| C/P | 0.9977 | likely_pathogenic | 0.9977 | pathogenic | -0.844 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| C/Q | 0.8974 | likely_pathogenic | 0.8889 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| C/R | 0.905 | likely_pathogenic | 0.9015 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.493118997 | None | None | I |
| C/S | 0.3307 | likely_benign | 0.3347 | benign | -0.679 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.384065948 | None | None | I |
| C/T | 0.5755 | likely_pathogenic | 0.5497 | ambiguous | -0.498 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| C/V | 0.6731 | likely_pathogenic | 0.6505 | pathogenic | -0.844 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | I |
| C/W | 0.8594 | likely_pathogenic | 0.847 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.490598675 | None | None | I |
| C/Y | 0.7699 | likely_pathogenic | 0.7565 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.808 | deleterious | N | 0.47898888 | None | None | I |
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.