Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21926 | 66001;66002;66003 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| N2AB | 20285 | 61078;61079;61080 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| N2A | 19358 | 58297;58298;58299 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| N2B | 12861 | 38806;38807;38808 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| Novex-1 | 12986 | 39181;39182;39183 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| Novex-2 | 13053 | 39382;39383;39384 | chr2:178583027;178583026;178583025 | chr2:179447754;179447753;179447752 |
| 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/M | rs145527033  |
-0.874 | 1.0 | N | 0.735 | 0.549 | None | gnomAD-2.1.1 | 3.85833E-04 | None | None | None | None | N | None | 2.99202E-03 | 7.15226E-04 | None | 0 | 0 | None | 6.59E-05 | None | 4.02E-05 | 3.95E-05 | 2.8393E-04 |
| V/M | rs145527033 |
-0.874 | 1.0 | N | 0.735 | 0.549 | None | gnomAD-3.1.2 | 7.95634E-04 | None | None | None | None | N | None | 2.60593E-03 | 5.89468E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| V/M | rs145527033 |
-0.874 | 1.0 | N | 0.735 | 0.549 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/M | rs145527033 |
-0.874 | 1.0 | N | 0.735 | 0.549 | None | gnomAD-4.0.0 | 1.8141E-04 | None | None | None | None | N | None | 2.37555E-03 | 6.52851E-04 | None | 0 | 2.2483E-05 | None | 0 | 0 | 4.75589E-05 | 5.53183E-05 | 2.08708E-04 |
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 | 0.3287 | likely_benign | 0.362 | ambiguous | -1.814 | Destabilizing | 0.543 | D | 0.289 | neutral | N | 0.493271792 | None | None | N |
| V/C | 0.8604 | likely_pathogenic | 0.8745 | pathogenic | -2.366 | Highly Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/D | 0.9867 | likely_pathogenic | 0.9886 | pathogenic | -2.894 | Highly Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| V/E | 0.975 | likely_pathogenic | 0.9781 | pathogenic | -2.826 | Highly Destabilizing | 0.998 | D | 0.692 | prob.neutral | D | 0.546372921 | None | None | N |
| V/F | 0.9122 | likely_pathogenic | 0.9145 | pathogenic | -1.59 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/G | 0.6805 | likely_pathogenic | 0.726 | pathogenic | -2.153 | Highly Destabilizing | 0.997 | D | 0.695 | prob.neutral | N | 0.516747776 | None | None | N |
| V/H | 0.9934 | likely_pathogenic | 0.9939 | pathogenic | -1.648 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| V/I | 0.151 | likely_benign | 0.146 | benign | -0.938 | Destabilizing | 0.99 | D | 0.501 | neutral | None | None | None | None | N |
| V/K | 0.9807 | likely_pathogenic | 0.984 | pathogenic | -1.694 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| V/L | 0.6245 | likely_pathogenic | 0.6099 | pathogenic | -0.938 | Destabilizing | 0.989 | D | 0.504 | neutral | N | 0.521885332 | None | None | N |
| V/M | 0.6031 | likely_pathogenic | 0.6267 | pathogenic | -1.193 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.519367896 | None | None | N |
| V/N | 0.9383 | likely_pathogenic | 0.9447 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| V/P | 0.922 | likely_pathogenic | 0.944 | pathogenic | -1.202 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/Q | 0.9695 | likely_pathogenic | 0.9716 | pathogenic | -2.087 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/R | 0.9713 | likely_pathogenic | 0.9746 | pathogenic | -1.209 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| V/S | 0.6169 | likely_pathogenic | 0.6539 | pathogenic | -2.421 | Highly Destabilizing | 0.995 | D | 0.669 | neutral | None | None | None | None | N |
| V/T | 0.442 | ambiguous | 0.4483 | ambiguous | -2.238 | Highly Destabilizing | 0.992 | D | 0.581 | neutral | None | None | None | None | N |
| V/W | 0.9986 | likely_pathogenic | 0.9985 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/Y | 0.9929 | likely_pathogenic | 0.993 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | 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.