Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19952 | 60079;60080;60081 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| N2AB | 18311 | 55156;55157;55158 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| N2A | 17384 | 52375;52376;52377 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| N2B | 10887 | 32884;32885;32886 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| Novex-1 | 11012 | 33259;33260;33261 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| Novex-2 | 11079 | 33460;33461;33462 | chr2:178592050;178592049;178592048 | chr2:179456777;179456776;179456775 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1314159875  |
-2.902 | 1.0 | N | 0.788 | 0.539 | 0.745165706587 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/D | rs1314159875 |
-2.902 | 1.0 | N | 0.788 | 0.539 | 0.745165706587 | gnomAD-4.0.0 | 1.59291E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86012E-06 | 0 | 0 |
| A/S | rs1037724422 |
None | 1.0 | N | 0.637 | 0.312 | 0.290590437066 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5787 | likely_pathogenic | 0.5728 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| A/D | 0.979 | likely_pathogenic | 0.9739 | pathogenic | -2.619 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | N | 0.508857969 | None | None | N |
| A/E | 0.9145 | likely_pathogenic | 0.9015 | pathogenic | -2.332 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/F | 0.8532 | likely_pathogenic | 0.8256 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| A/G | 0.2875 | likely_benign | 0.2697 | benign | -2.366 | Highly Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.498008642 | None | None | N |
| A/H | 0.9396 | likely_pathogenic | 0.9283 | pathogenic | -2.375 | Highly Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| A/I | 0.8455 | likely_pathogenic | 0.824 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/K | 0.973 | likely_pathogenic | 0.9697 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| A/L | 0.7295 | likely_pathogenic | 0.7175 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| A/M | 0.6674 | likely_pathogenic | 0.6301 | pathogenic | -0.884 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/N | 0.9427 | likely_pathogenic | 0.9308 | pathogenic | -1.971 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/P | 0.998 | likely_pathogenic | 0.9978 | pathogenic | -0.913 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.509618437 | None | None | N |
| A/Q | 0.8259 | likely_pathogenic | 0.8114 | pathogenic | -1.585 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/R | 0.917 | likely_pathogenic | 0.9128 | pathogenic | -1.649 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| A/S | 0.1829 | likely_benign | 0.1693 | benign | -2.278 | Highly Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.481040708 | None | None | N |
| A/T | 0.4096 | ambiguous | 0.3816 | ambiguous | -1.87 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.501722625 | None | None | N |
| A/V | 0.5784 | likely_pathogenic | 0.5458 | ambiguous | -0.913 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.498567676 | None | None | N |
| A/W | 0.9747 | likely_pathogenic | 0.9709 | pathogenic | -1.418 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| A/Y | 0.9225 | likely_pathogenic | 0.9105 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.771 | 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.