Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25340 | 76243;76244;76245 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| N2AB | 23699 | 71320;71321;71322 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| N2A | 22772 | 68539;68540;68541 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| N2B | 16275 | 49048;49049;49050 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| Novex-1 | 16400 | 49423;49424;49425 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| Novex-2 | 16467 | 49624;49625;49626 | chr2:178570114;178570113;178570112 | chr2:179434841;179434840;179434839 |
| 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/D | rs200287703  |
-3.521 | 0.979 | N | 0.758 | 0.46 | None | gnomAD-2.1.1 | 2.21682E-04 | None | None | None | None | N | None | 2.06731E-03 | 3.11333E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40449E-04 |
| V/D | rs200287703 |
-3.521 | 0.979 | N | 0.758 | 0.46 | None | gnomAD-3.1.2 | 6.2491E-04 | None | None | None | None | N | None | 2.10145E-03 | 4.58595E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| V/D | rs200287703 |
-3.521 | 0.979 | N | 0.758 | 0.46 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/D | rs200287703 |
-3.521 | 0.979 | N | 0.758 | 0.46 | None | gnomAD-4.0.0 | 1.30157E-04 | None | None | None | None | N | None | 2.46772E-03 | 3.0002E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.12061E-04 |
| V/I | rs1207970602 |
-0.821 | 0.003 | N | 0.263 | 0.073 | 0.268660756437 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1207970602 |
-0.821 | 0.003 | N | 0.263 | 0.073 | 0.268660756437 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1207970602 |
-0.821 | 0.003 | N | 0.263 | 0.073 | 0.268660756437 | gnomAD-4.0.0 | 3.84504E-06 | None | None | None | None | N | None | 3.38513E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84527E-05 |
| V/L | None | None | 0.164 | N | 0.523 | 0.109 | 0.37550373646 | gnomAD-4.0.0 | 1.59191E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-05 | 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 | 0.3471 | ambiguous | 0.3957 | ambiguous | -2.36 | Highly Destabilizing | 0.472 | N | 0.671 | neutral | N | 0.508397881 | None | None | N |
| V/C | 0.602 | likely_pathogenic | 0.6698 | pathogenic | -1.771 | Destabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/D | 0.7772 | likely_pathogenic | 0.7757 | pathogenic | -2.973 | Highly Destabilizing | 0.979 | D | 0.758 | deleterious | N | 0.521961824 | None | None | N |
| V/E | 0.644 | likely_pathogenic | 0.6403 | pathogenic | -2.767 | Highly Destabilizing | 0.953 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/F | 0.1329 | likely_benign | 0.1558 | benign | -1.35 | Destabilizing | 0.792 | D | 0.747 | deleterious | N | 0.500202472 | None | None | N |
| V/G | 0.4878 | ambiguous | 0.5351 | ambiguous | -2.868 | Highly Destabilizing | 0.939 | D | 0.737 | prob.delet. | N | 0.49424598 | None | None | N |
| V/H | 0.5329 | ambiguous | 0.5898 | pathogenic | -2.48 | Highly Destabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| V/I | 0.065 | likely_benign | 0.0723 | benign | -0.934 | Destabilizing | 0.003 | N | 0.263 | neutral | N | 0.388783908 | None | None | N |
| V/K | 0.6528 | likely_pathogenic | 0.6743 | pathogenic | -2.032 | Highly Destabilizing | 0.953 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/L | 0.1492 | likely_benign | 0.1856 | benign | -0.934 | Destabilizing | 0.164 | N | 0.523 | neutral | N | 0.461086724 | None | None | N |
| V/M | 0.1433 | likely_benign | 0.1779 | benign | -0.96 | Destabilizing | 0.91 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/N | 0.4125 | ambiguous | 0.4735 | ambiguous | -2.308 | Highly Destabilizing | 0.984 | D | 0.767 | deleterious | None | None | None | None | N |
| V/P | 0.982 | likely_pathogenic | 0.9826 | pathogenic | -1.385 | Destabilizing | 0.984 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/Q | 0.4701 | ambiguous | 0.5236 | ambiguous | -2.188 | Highly Destabilizing | 0.984 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/R | 0.5309 | ambiguous | 0.5478 | ambiguous | -1.728 | Destabilizing | 0.953 | D | 0.768 | deleterious | None | None | None | None | N |
| V/S | 0.3431 | ambiguous | 0.4109 | ambiguous | -2.896 | Highly Destabilizing | 0.953 | D | 0.718 | prob.delet. | None | None | None | None | N |
| V/T | 0.2813 | likely_benign | 0.3365 | benign | -2.564 | Highly Destabilizing | 0.742 | D | 0.708 | prob.delet. | None | None | None | None | N |
| V/W | 0.742 | likely_pathogenic | 0.7897 | pathogenic | -1.846 | Destabilizing | 0.02 | N | 0.671 | neutral | None | None | None | None | N |
| V/Y | 0.4202 | ambiguous | 0.4697 | ambiguous | -1.535 | Destabilizing | 0.835 | D | 0.74 | deleterious | 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.