Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17376 | 52351;52352;52353 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| N2AB | 15735 | 47428;47429;47430 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| N2A | 14808 | 44647;44648;44649 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| N2B | 8311 | 25156;25157;25158 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| Novex-1 | 8436 | 25531;25532;25533 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| Novex-2 | 8503 | 25732;25733;25734 | chr2:178608885;178608884;178608883 | chr2:179473612;179473611;179473610 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs761660658  |
-1.129 | 0.217 | N | 0.38 | 0.232 | 0.0954503805726 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87687E-04 | 0 | 0 |
| F/L | rs761660658 |
-1.129 | 0.217 | N | 0.38 | 0.232 | 0.0954503805726 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 1.88253E-04 | 0 | 0 | 0 | 0 |
| F/L | rs761660658 |
-1.129 | 0.217 | N | 0.38 | 0.232 | 0.0954503805726 | gnomAD-4.0.0 | 5.14467E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.46496E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9783 | likely_pathogenic | 0.9825 | pathogenic | -2.426 | Highly Destabilizing | 0.996 | D | 0.771 | deleterious | None | None | None | None | I |
| F/C | 0.9019 | likely_pathogenic | 0.9144 | pathogenic | -1.24 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.477320267 | None | None | I |
| F/D | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -3.099 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| F/E | 0.9978 | likely_pathogenic | 0.9982 | pathogenic | -2.872 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| F/G | 0.9933 | likely_pathogenic | 0.9946 | pathogenic | -2.878 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| F/H | 0.9887 | likely_pathogenic | 0.9894 | pathogenic | -1.714 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| F/I | 0.5016 | ambiguous | 0.5171 | ambiguous | -0.951 | Destabilizing | 0.978 | D | 0.734 | prob.delet. | N | 0.425992715 | None | None | I |
| F/K | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -1.691 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| F/L | 0.8853 | likely_pathogenic | 0.9016 | pathogenic | -0.951 | Destabilizing | 0.217 | N | 0.38 | neutral | N | 0.414900569 | None | None | I |
| F/M | 0.7371 | likely_pathogenic | 0.7601 | pathogenic | -0.668 | Destabilizing | 0.998 | D | 0.734 | prob.delet. | None | None | None | None | I |
| F/N | 0.9951 | likely_pathogenic | 0.9955 | pathogenic | -2.272 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| F/P | 0.9934 | likely_pathogenic | 0.9947 | pathogenic | -1.455 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| F/Q | 0.9967 | likely_pathogenic | 0.997 | pathogenic | -2.144 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| F/R | 0.9954 | likely_pathogenic | 0.9955 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| F/S | 0.9908 | likely_pathogenic | 0.9916 | pathogenic | -2.79 | Highly Destabilizing | 0.999 | D | 0.812 | deleterious | N | 0.470229922 | None | None | I |
| F/T | 0.973 | likely_pathogenic | 0.9785 | pathogenic | -2.447 | Highly Destabilizing | 0.999 | D | 0.796 | deleterious | None | None | None | None | I |
| F/V | 0.5792 | likely_pathogenic | 0.6107 | pathogenic | -1.455 | Destabilizing | 0.978 | D | 0.717 | prob.delet. | N | 0.424141702 | None | None | I |
| F/W | 0.8673 | likely_pathogenic | 0.8643 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| F/Y | 0.6509 | likely_pathogenic | 0.6519 | pathogenic | -0.488 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | N | 0.488423083 | 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.