Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35930 | 108013;108014;108015 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| N2AB | 34289 | 103090;103091;103092 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| N2A | 33362 | 100309;100310;100311 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| N2B | 26865 | 80818;80819;80820 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| Novex-1 | 26990 | 81193;81194;81195 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| Novex-2 | 27057 | 81394;81395;81396 | chr2:178527200;178527199;178527198 | chr2:179391927;179391926;179391925 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | rs1018591024  |
-2.172 | 1.0 | D | 0.836 | 0.938 | 0.942593547874 |
Zheng (2016)
| None |
LGMD2J 
|
hom | None | -0.843(OBSL1) -1.308(OBSCN) | N | WES prioritisation of single 5-generation CN family; co-segregation within family (recessive inheritance, n = 3, 3 affected, (6 total)) | None | None | None | None | None | None | None | None | None | None | None |
| W/R | rs1018591024 |
-2.172 | 1.0 | D | 0.836 | 0.938 | 0.942593547874 | gnomAD-4.0.0 | 2.7366E-06 | None | None | None | -0.843(OBSL1) -1.308(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59762E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9929 | likely_pathogenic | 0.9912 | pathogenic | -3.194 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | -0.122(OBSL1) -0.511(OBSCN) | N |
| W/C | 0.9977 | likely_pathogenic | 0.9974 | pathogenic | -2.202 | Highly Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.652453558 | None | -0.549(OBSL1) -0.838(OBSCN) | N |
| W/D | 0.9994 | likely_pathogenic | 0.9991 | pathogenic | -3.025 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | -0.618(OBSL1) -1.016(OBSCN) | N |
| W/E | 0.999 | likely_pathogenic | 0.9985 | pathogenic | -2.893 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | -0.653(OBSL1) -1.063(OBSCN) | N |
| W/F | 0.6637 | likely_pathogenic | 0.622 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | -0.558(OBSL1) -0.735(OBSCN) | N |
| W/G | 0.9831 | likely_pathogenic | 0.9786 | pathogenic | -3.456 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.700542001 | None | -0.078(OBSL1) -0.454(OBSCN) | N |
| W/H | 0.9975 | likely_pathogenic | 0.9965 | pathogenic | -2.395 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | -0.33(OBSL1) -0.484(OBSCN) | N |
| W/I | 0.9573 | likely_pathogenic | 0.9483 | pathogenic | -2.205 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | -0.316(OBSL1) -0.728(OBSCN) | N |
| W/K | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -2.655 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | -0.47(OBSL1) -0.955(OBSCN) | N |
| W/L | 0.9105 | likely_pathogenic | 0.8929 | pathogenic | -2.205 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.700542001 | None | -0.316(OBSL1) -0.728(OBSCN) | N |
| W/M | 0.9883 | likely_pathogenic | 0.9858 | pathogenic | -1.863 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | -0.598(OBSL1) -0.853(OBSCN) | N |
| W/N | 0.9993 | likely_pathogenic | 0.9991 | pathogenic | -3.319 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | -0.568(OBSL1) -1.104(OBSCN) | N |
| W/P | 0.9987 | likely_pathogenic | 0.9983 | pathogenic | -2.564 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | -0.242(OBSL1) -0.649(OBSCN) | N |
| W/Q | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -3.105 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | -0.557(OBSL1) -1.09(OBSCN) | N |
| W/R | 0.9987 | likely_pathogenic | 0.9983 | pathogenic | -2.404 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.700743806 | None | -0.843(OBSL1) -1.308(OBSCN) | N |
| W/S | 0.9938 | likely_pathogenic | 0.9923 | pathogenic | -3.602 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | D | 0.700743805 | None | -0.21(OBSL1) -0.647(OBSCN) | N |
| W/T | 0.9952 | likely_pathogenic | 0.9937 | pathogenic | -3.4 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | -0.251(OBSL1) -0.701(OBSCN) | N |
| W/V | 0.9611 | likely_pathogenic | 0.9523 | pathogenic | -2.564 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | -0.242(OBSL1) -0.649(OBSCN) | N |
| W/Y | 0.923 | likely_pathogenic | 0.9118 | pathogenic | -1.824 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | -0.644(OBSL1) -0.843(OBSCN) | 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.