Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2332 | 7219;7220;7221 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| N2AB | 2332 | 7219;7220;7221 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| N2A | 2332 | 7219;7220;7221 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| N2B | 2286 | 7081;7082;7083 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| Novex-1 | 2286 | 7081;7082;7083 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| Novex-2 | 2286 | 7081;7082;7083 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
| Novex-3 | 2332 | 7219;7220;7221 | chr2:178774270;178774269;178774268 | chr2:179638997;179638996;179638995 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs749655939  |
-0.473 | 1.0 | D | 0.785 | 0.902 | 0.729455935219 | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.55E-05 | 0 |
| D/G | rs749655939 |
-0.473 | 1.0 | D | 0.785 | 0.902 | 0.729455935219 | gnomAD-4.0.0 | 6.1567E-06 | None | None | None | None | N | None | 5.97479E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29517E-06 | 0 | 0 |
| D/N | rs771180382 |
-0.892 | 1.0 | D | 0.779 | 0.837 | 0.738802388025 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| D/N | rs771180382 |
-0.892 | 1.0 | D | 0.779 | 0.837 | 0.738802388025 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs771180382 |
-0.892 | 1.0 | D | 0.779 | 0.837 | 0.738802388025 | gnomAD-4.0.0 | 7.68433E-06 | None | None | None | None | N | None | 0 | 6.78081E-05 | None | 0 | 0 | None | 0 | 0 | 4.78361E-06 | 0 | 0 |
| D/Y | rs771180382 |
0.42 | 1.0 | D | 0.851 | 0.906 | 0.911509777594 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/Y | rs771180382 |
0.42 | 1.0 | D | 0.851 | 0.906 | 0.911509777594 | gnomAD-4.0.0 | 1.59057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9212 | likely_pathogenic | 0.9397 | pathogenic | 0.262 | Stabilizing | 1.0 | D | 0.854 | deleterious | D | 0.739678468 | None | None | N |
| D/C | 0.9759 | likely_pathogenic | 0.9814 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| D/E | 0.8452 | likely_pathogenic | 0.8801 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.576 | neutral | D | 0.740753703 | None | None | N |
| D/F | 0.9826 | likely_pathogenic | 0.9869 | pathogenic | 0.534 | Stabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| D/G | 0.9314 | likely_pathogenic | 0.9449 | pathogenic | -0.211 | Destabilizing | 1.0 | D | 0.785 | deleterious | D | 0.738933181 | None | None | N |
| D/H | 0.9063 | likely_pathogenic | 0.9278 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.813 | deleterious | D | 0.642785792 | None | None | N |
| D/I | 0.9712 | likely_pathogenic | 0.9788 | pathogenic | 1.548 | Stabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| D/K | 0.9855 | likely_pathogenic | 0.9879 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| D/L | 0.9681 | likely_pathogenic | 0.9754 | pathogenic | 1.548 | Stabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| D/M | 0.9772 | likely_pathogenic | 0.9826 | pathogenic | 2.095 | Highly Stabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| D/N | 0.6529 | likely_pathogenic | 0.689 | pathogenic | -1.06 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.741180589 | None | None | N |
| D/P | 0.9989 | likely_pathogenic | 0.9991 | pathogenic | 1.148 | Stabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| D/Q | 0.9622 | likely_pathogenic | 0.9706 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| D/R | 0.9915 | likely_pathogenic | 0.9931 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| D/S | 0.8636 | likely_pathogenic | 0.8892 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| D/T | 0.9621 | likely_pathogenic | 0.9713 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| D/V | 0.9372 | likely_pathogenic | 0.9519 | pathogenic | 1.148 | Stabilizing | 1.0 | D | 0.853 | deleterious | D | 0.738929176 | None | None | N |
| D/W | 0.9976 | likely_pathogenic | 0.9982 | pathogenic | 0.205 | Stabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| D/Y | 0.8922 | likely_pathogenic | 0.9136 | pathogenic | 0.641 | Stabilizing | 1.0 | D | 0.851 | deleterious | D | 0.739011396 | 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.