Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35971 | 108136;108137;108138 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| N2AB | 34330 | 103213;103214;103215 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| N2A | 33403 | 100432;100433;100434 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| N2B | 26906 | 80941;80942;80943 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| Novex-1 | 27031 | 81316;81317;81318 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| Novex-2 | 27098 | 81517;81518;81519 | chr2:178527077;178527076;178527075 | chr2:179391804;179391803;179391802 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/V | None | None | 0.999 | N | 0.709 | 0.302 | 0.430239905395 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | -1.257(OBSL1) -1.035(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85765E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9271 | likely_pathogenic | 0.9283 | pathogenic | -2.639 | Highly Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | -1.005(OBSL1) -0.699(OBSCN) | N |
| L/C | 0.9339 | likely_pathogenic | 0.9351 | pathogenic | -2.34 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | -1.598(OBSL1) -0.92(OBSCN) | N |
| L/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -2.406 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | -0.923(OBSL1) -0.628(OBSCN) | N |
| L/E | 0.9973 | likely_pathogenic | 0.9963 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | -1.03(OBSL1) -0.782(OBSCN) | N |
| L/F | 0.7675 | likely_pathogenic | 0.7752 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | -1.838(OBSL1) -1.736(OBSCN) | N |
| L/G | 0.9938 | likely_pathogenic | 0.9932 | pathogenic | -3.158 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | -0.893(OBSL1) -0.543(OBSCN) | N |
| L/H | 0.9951 | likely_pathogenic | 0.9931 | pathogenic | -2.423 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | -1.619(OBSL1) -0.578(OBSCN) | N |
| L/I | 0.172 | likely_benign | 0.2031 | benign | -1.162 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | -1.393(OBSL1) -1.211(OBSCN) | N |
| L/K | 0.995 | likely_pathogenic | 0.9928 | pathogenic | -1.918 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | -1.925(OBSL1) -0.766(OBSCN) | N |
| L/M | 0.4404 | ambiguous | 0.4661 | ambiguous | -1.242 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.460998486 | None | -1.562(OBSL1) -1.451(OBSCN) | N |
| L/N | 0.998 | likely_pathogenic | 0.9972 | pathogenic | -2.135 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | -1.439(OBSL1) -0.6(OBSCN) | N |
| L/P | 0.9975 | likely_pathogenic | 0.9966 | pathogenic | -1.633 | Destabilizing | 1.0 | D | 0.895 | deleterious | N | 0.48438266 | None | -1.257(OBSL1) -1.035(OBSCN) | N |
| L/Q | 0.9896 | likely_pathogenic | 0.9853 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | N | 0.48438266 | None | -1.47(OBSL1) -0.707(OBSCN) | N |
| L/R | 0.9879 | likely_pathogenic | 0.9821 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.89 | deleterious | N | 0.48438266 | None | -2.171(OBSL1) -0.851(OBSCN) | N |
| L/S | 0.9948 | likely_pathogenic | 0.9939 | pathogenic | -2.971 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | -1.356(OBSL1) -0.171(OBSCN) | N |
| L/T | 0.976 | likely_pathogenic | 0.9723 | pathogenic | -2.633 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | -1.501(OBSL1) -0.367(OBSCN) | N |
| L/V | 0.1825 | likely_benign | 0.2037 | benign | -1.633 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.47240729 | None | -1.257(OBSL1) -1.035(OBSCN) | N |
| L/W | 0.9891 | likely_pathogenic | 0.987 | pathogenic | -1.957 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | -2.281(OBSL1) -2.233(OBSCN) | N |
| L/Y | 0.9872 | likely_pathogenic | 0.9861 | pathogenic | -1.726 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | -1.96(OBSL1) -1.806(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.