Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26562 | 79909;79910;79911 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| N2AB | 24921 | 74986;74987;74988 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| N2A | 23994 | 72205;72206;72207 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| N2B | 17497 | 52714;52715;52716 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| Novex-1 | 17622 | 53089;53090;53091 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| Novex-2 | 17689 | 53290;53291;53292 | chr2:178566448;178566447;178566446 | chr2:179431175;179431174;179431173 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs538960023  |
-0.873 | 1.0 | N | 0.796 | 0.263 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.92208E-04 | None | 4.02E-05 | 2.35E-05 | 0 |
| R/Q | rs538960023 |
-0.873 | 1.0 | N | 0.796 | 0.263 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 2.94E-05 | 2.07211E-04 | 0 |
| R/Q | rs538960023 |
-0.873 | 1.0 | N | 0.796 | 0.263 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/Q | rs538960023 |
-0.873 | 1.0 | N | 0.796 | 0.263 | None | gnomAD-4.0.0 | 3.71881E-05 | None | None | None | None | N | None | 1.33316E-05 | 1.66689E-05 | None | 0 | 0 | None | 7.83822E-05 | 0 | 2.11923E-05 | 2.63528E-04 | 6.40328E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6147 | likely_pathogenic | 0.6209 | pathogenic | -1.711 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| R/C | 0.2006 | likely_benign | 0.2085 | benign | -1.714 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| R/D | 0.8965 | likely_pathogenic | 0.9083 | pathogenic | -0.779 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| R/E | 0.5903 | likely_pathogenic | 0.5938 | pathogenic | -0.585 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/F | 0.8232 | likely_pathogenic | 0.8363 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| R/G | 0.5611 | ambiguous | 0.5929 | pathogenic | -2.063 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.528383212 | None | None | N |
| R/H | 0.1462 | likely_benign | 0.1567 | benign | -1.981 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| R/I | 0.5341 | ambiguous | 0.5435 | ambiguous | -0.71 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| R/K | 0.1582 | likely_benign | 0.1671 | benign | -1.358 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/L | 0.4698 | ambiguous | 0.4745 | ambiguous | -0.71 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.50226356 | None | None | N |
| R/M | 0.5152 | ambiguous | 0.5274 | ambiguous | -1.133 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| R/N | 0.6899 | likely_pathogenic | 0.7135 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/P | 0.9903 | likely_pathogenic | 0.9925 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.539993007 | None | None | N |
| R/Q | 0.1096 | likely_benign | 0.1116 | benign | -1.133 | Destabilizing | 1.0 | D | 0.796 | deleterious | N | 0.467269591 | None | None | N |
| R/S | 0.6241 | likely_pathogenic | 0.6385 | pathogenic | -2.074 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/T | 0.4529 | ambiguous | 0.4815 | ambiguous | -1.669 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/V | 0.58 | likely_pathogenic | 0.5924 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| R/W | 0.3953 | ambiguous | 0.4274 | ambiguous | -0.645 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/Y | 0.6171 | likely_pathogenic | 0.6421 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.853 | 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.