Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35961 | 108106;108107;108108 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| N2AB | 34320 | 103183;103184;103185 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| N2A | 33393 | 100402;100403;100404 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| N2B | 26896 | 80911;80912;80913 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| Novex-1 | 27021 | 81286;81287;81288 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| Novex-2 | 27088 | 81487;81488;81489 | chr2:178527107;178527106;178527105 | chr2:179391834;179391833;179391832 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.581 | N | 0.515 | 0.403 | 0.652866637519 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | -0.982(OBSL1) -0.734(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/I | None | -1.202 | 0.024 | N | 0.314 | 0.114 | None | gnomAD-2.1.1 | 4.01E-06 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | None | -1.202 | 0.024 | N | 0.314 | 0.114 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.79386E-04 |
| V/I | None | -1.202 | 0.024 | N | 0.314 | 0.114 | None | gnomAD-4.0.0 | 9.29492E-06 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 2.67023E-05 | 3.33367E-05 | None | 0 | 0 | None | 0 | 0 | 5.9329E-06 | 1.09794E-05 | 4.80323E-05 |
| V/L | rs780886524  |
-1.197 | 0.201 | D | 0.489 | 0.344 | 0.503311249505 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 1.65235E-04 |
| V/L | rs780886524 |
-1.197 | 0.201 | D | 0.489 | 0.344 | 0.503311249505 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| V/L | rs780886524 |
-1.197 | 0.201 | D | 0.489 | 0.344 | 0.503311249505 | gnomAD-4.0.0 | 1.85898E-06 | None | None | None | -1.469(OBSL1) -1.143(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54267E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7078 | likely_pathogenic | 0.78 | pathogenic | -2.359 | Highly Destabilizing | 0.581 | D | 0.515 | neutral | N | 0.509702682 | None | -0.982(OBSL1) -0.734(OBSCN) | N |
| V/C | 0.9528 | likely_pathogenic | 0.9627 | pathogenic | -2.291 | Highly Destabilizing | 0.993 | D | 0.72 | prob.delet. | None | None | None | -1.554(OBSL1) -1.383(OBSCN) | N |
| V/D | 0.9926 | likely_pathogenic | 0.9936 | pathogenic | -3.369 | Highly Destabilizing | 0.929 | D | 0.799 | deleterious | None | None | None | -1.344(OBSL1) -1.607(OBSCN) | N |
| V/E | 0.9843 | likely_pathogenic | 0.9847 | pathogenic | -3.187 | Highly Destabilizing | 0.908 | D | 0.77 | deleterious | D | 0.554437543 | None | -1.528(OBSL1) -1.794(OBSCN) | N |
| V/F | 0.9111 | likely_pathogenic | 0.928 | pathogenic | -1.397 | Destabilizing | 0.866 | D | 0.787 | deleterious | None | None | None | -1.351(OBSL1) -0.775(OBSCN) | N |
| V/G | 0.8911 | likely_pathogenic | 0.9095 | pathogenic | -2.834 | Highly Destabilizing | 0.908 | D | 0.776 | deleterious | N | 0.518229033 | None | -0.841(OBSL1) -0.622(OBSCN) | N |
| V/H | 0.9964 | likely_pathogenic | 0.9973 | pathogenic | -2.363 | Highly Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | -1.185(OBSL1) -0.739(OBSCN) | N |
| V/I | 0.1235 | likely_benign | 0.1429 | benign | -1.037 | Destabilizing | 0.024 | N | 0.314 | neutral | N | 0.509222679 | None | -1.469(OBSL1) -1.143(OBSCN) | N |
| V/K | 0.99 | likely_pathogenic | 0.9898 | pathogenic | -2.006 | Highly Destabilizing | 0.929 | D | 0.771 | deleterious | None | None | None | -2.292(OBSL1) -1.931(OBSCN) | N |
| V/L | 0.7518 | likely_pathogenic | 0.8087 | pathogenic | -1.037 | Destabilizing | 0.201 | N | 0.489 | neutral | D | 0.539393658 | None | -1.469(OBSL1) -1.143(OBSCN) | N |
| V/M | 0.6924 | likely_pathogenic | 0.7383 | pathogenic | -1.315 | Destabilizing | 0.866 | D | 0.795 | deleterious | None | None | None | -1.346(OBSL1) -1.155(OBSCN) | N |
| V/N | 0.9748 | likely_pathogenic | 0.9797 | pathogenic | -2.364 | Highly Destabilizing | 0.976 | D | 0.795 | deleterious | None | None | None | -1.591(OBSL1) -1.316(OBSCN) | N |
| V/P | 0.9696 | likely_pathogenic | 0.9833 | pathogenic | -1.454 | Destabilizing | 0.976 | D | 0.793 | deleterious | None | None | None | -1.298(OBSL1) -0.996(OBSCN) | N |
| V/Q | 0.9853 | likely_pathogenic | 0.9874 | pathogenic | -2.29 | Highly Destabilizing | 0.976 | D | 0.774 | deleterious | None | None | None | -1.676(OBSL1) -1.421(OBSCN) | N |
| V/R | 0.9816 | likely_pathogenic | 0.9805 | pathogenic | -1.682 | Destabilizing | 0.929 | D | 0.791 | deleterious | None | None | None | -2.492(OBSL1) -2.106(OBSCN) | N |
| V/S | 0.8937 | likely_pathogenic | 0.9141 | pathogenic | -2.906 | Highly Destabilizing | 0.929 | D | 0.773 | deleterious | None | None | None | -1.367(OBSL1) -0.98(OBSCN) | N |
| V/T | 0.7213 | likely_pathogenic | 0.7817 | pathogenic | -2.598 | Highly Destabilizing | 0.648 | D | 0.713 | prob.delet. | None | None | None | -1.569(OBSL1) -1.165(OBSCN) | N |
| V/W | 0.9986 | likely_pathogenic | 0.9988 | pathogenic | -1.847 | Destabilizing | 0.993 | D | 0.725 | prob.delet. | None | None | None | -1.63(OBSL1) -0.985(OBSCN) | N |
| V/Y | 0.9934 | likely_pathogenic | 0.9944 | pathogenic | -1.569 | Destabilizing | 0.929 | D | 0.797 | deleterious | None | None | None | -1.425(OBSL1) -0.8(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.