Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17447 | 52564;52565;52566 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| N2AB | 15806 | 47641;47642;47643 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| N2A | 14879 | 44860;44861;44862 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| N2B | 8382 | 25369;25370;25371 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| Novex-1 | 8507 | 25744;25745;25746 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| Novex-2 | 8574 | 25945;25946;25947 | chr2:178608672;178608671;178608670 | chr2:179473399;179473398;179473397 |
| 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 | None | None | 0.142 | D | 0.619 | 0.713 | 0.529661991002 | gnomAD-4.0.0 | 5.47962E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.20051E-06 | 0 | 0 |
| A/G | rs758092362  |
-2.451 | 0.958 | D | 0.625 | 0.591 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| A/G | rs758092362 |
-2.451 | 0.958 | D | 0.625 | 0.591 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/G | rs758092362 |
-2.451 | 0.958 | D | 0.625 | 0.591 | None | gnomAD-4.0.0 | 6.20359E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56416E-05 | 0 | 5.93736E-06 | 0 | 3.20688E-05 |
| A/T | rs1367567526 |
-1.906 | 0.958 | D | 0.732 | 0.632 | 0.516050471323 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| A/T | rs1367567526 |
-1.906 | 0.958 | D | 0.732 | 0.632 | 0.516050471323 | gnomAD-4.0.0 | 7.20193E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-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 | 0.92 | likely_pathogenic | 0.9239 | pathogenic | -1.953 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| A/D | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -2.972 | Highly Destabilizing | 0.142 | N | 0.619 | neutral | D | 0.565648356 | None | None | N |
| A/E | 0.9968 | likely_pathogenic | 0.9973 | pathogenic | -2.765 | Highly Destabilizing | 0.938 | D | 0.774 | deleterious | None | None | None | None | N |
| A/F | 0.9959 | likely_pathogenic | 0.9968 | pathogenic | -0.677 | Destabilizing | 0.998 | D | 0.887 | deleterious | None | None | None | None | N |
| A/G | 0.3858 | ambiguous | 0.3978 | ambiguous | -2.131 | Highly Destabilizing | 0.958 | D | 0.625 | neutral | D | 0.526526557 | None | None | N |
| A/H | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -1.888 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| A/I | 0.9926 | likely_pathogenic | 0.9945 | pathogenic | -0.66 | Destabilizing | 0.995 | D | 0.831 | deleterious | None | None | None | None | N |
| A/K | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.45 | Destabilizing | 0.991 | D | 0.796 | deleterious | None | None | None | None | N |
| A/L | 0.9679 | likely_pathogenic | 0.9723 | pathogenic | -0.66 | Destabilizing | 0.995 | D | 0.781 | deleterious | None | None | None | None | N |
| A/M | 0.9838 | likely_pathogenic | 0.9856 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/N | 0.9963 | likely_pathogenic | 0.9962 | pathogenic | -1.934 | Destabilizing | 0.982 | D | 0.845 | deleterious | None | None | None | None | N |
| A/P | 0.9592 | likely_pathogenic | 0.9503 | pathogenic | -0.99 | Destabilizing | 0.994 | D | 0.829 | deleterious | D | 0.55429205 | None | None | N |
| A/Q | 0.9933 | likely_pathogenic | 0.9943 | pathogenic | -1.7 | Destabilizing | 0.995 | D | 0.831 | deleterious | None | None | None | None | N |
| A/R | 0.9959 | likely_pathogenic | 0.9967 | pathogenic | -1.482 | Destabilizing | 0.995 | D | 0.84 | deleterious | None | None | None | None | N |
| A/S | 0.5134 | ambiguous | 0.5126 | ambiguous | -2.245 | Highly Destabilizing | 0.958 | D | 0.607 | neutral | N | 0.507546474 | None | None | N |
| A/T | 0.9328 | likely_pathogenic | 0.9385 | pathogenic | -1.937 | Destabilizing | 0.958 | D | 0.732 | prob.delet. | D | 0.550236218 | None | None | N |
| A/V | 0.9508 | likely_pathogenic | 0.9615 | pathogenic | -0.99 | Destabilizing | 0.979 | D | 0.731 | prob.delet. | D | 0.552010645 | None | None | N |
| A/W | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.24 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| A/Y | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -0.984 | Destabilizing | 1.0 | D | 0.887 | 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.