Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31176 | 93751;93752;93753 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| N2AB | 29535 | 88828;88829;88830 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| N2A | 28608 | 86047;86048;86049 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| N2B | 22111 | 66556;66557;66558 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| Novex-1 | 22236 | 66931;66932;66933 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| Novex-2 | 22303 | 67132;67133;67134 | chr2:178548100;178548099;178548098 | chr2:179412827;179412826;179412825 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs773083742  |
-1.494 | 1.0 | D | 0.861 | 0.849 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| L/P | rs773083742 |
-1.494 | 1.0 | D | 0.861 | 0.849 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| L/P | rs773083742 |
-1.494 | 1.0 | D | 0.861 | 0.849 | None | gnomAD-4.0.0 | 3.28614E-05 | None | None | None | None | N | None | 4.82462E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.41047E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8218 | likely_pathogenic | 0.8559 | pathogenic | -2.418 | Highly Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| L/C | 0.8105 | likely_pathogenic | 0.8779 | pathogenic | -1.909 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/D | 0.9976 | likely_pathogenic | 0.9967 | pathogenic | -1.884 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/E | 0.9871 | likely_pathogenic | 0.9834 | pathogenic | -1.708 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| L/F | 0.8551 | likely_pathogenic | 0.8447 | pathogenic | -1.513 | Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.641991941 | None | None | N |
| L/G | 0.9515 | likely_pathogenic | 0.9486 | pathogenic | -2.931 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/H | 0.9821 | likely_pathogenic | 0.9765 | pathogenic | -2.105 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | D | 0.658818519 | None | None | N |
| L/I | 0.461 | ambiguous | 0.5208 | ambiguous | -0.975 | Destabilizing | 0.999 | D | 0.837 | deleterious | D | 0.611730174 | None | None | N |
| L/K | 0.9816 | likely_pathogenic | 0.9742 | pathogenic | -1.73 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/M | 0.3849 | ambiguous | 0.4598 | ambiguous | -0.966 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/N | 0.9806 | likely_pathogenic | 0.9808 | pathogenic | -1.909 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/P | 0.981 | likely_pathogenic | 0.9729 | pathogenic | -1.432 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.658818519 | None | None | N |
| L/Q | 0.95 | likely_pathogenic | 0.9441 | pathogenic | -1.846 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| L/R | 0.9637 | likely_pathogenic | 0.9437 | pathogenic | -1.345 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.633280407 | None | None | N |
| L/S | 0.9782 | likely_pathogenic | 0.9811 | pathogenic | -2.755 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/T | 0.8981 | likely_pathogenic | 0.9095 | pathogenic | -2.421 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| L/V | 0.4145 | ambiguous | 0.4995 | ambiguous | -1.432 | Destabilizing | 0.999 | D | 0.846 | deleterious | D | 0.581195163 | None | None | N |
| L/W | 0.9789 | likely_pathogenic | 0.9685 | pathogenic | -1.689 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| L/Y | 0.9796 | likely_pathogenic | 0.9748 | pathogenic | -1.443 | Destabilizing | 1.0 | D | 0.835 | 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.