Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19554 | 58885;58886;58887 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| N2AB | 17913 | 53962;53963;53964 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| N2A | 16986 | 51181;51182;51183 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| N2B | 10489 | 31690;31691;31692 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| Novex-1 | 10614 | 32065;32066;32067 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| Novex-2 | 10681 | 32266;32267;32268 | chr2:178593640;178593639;178593638 | chr2:179458367;179458366;179458365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs879139698  |
None | 0.993 | N | 0.343 | 0.379 | 0.631849437455 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 1.26695E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs974431132 |
-3.572 | 1.0 | N | 0.785 | 0.524 | 0.798160069708 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs974431132 |
-3.572 | 1.0 | N | 0.785 | 0.524 | 0.798160069708 | gnomAD-4.0.0 | 3.18593E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86664E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9772 | likely_pathogenic | 0.9729 | pathogenic | -3.374 | Highly Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| I/C | 0.9639 | likely_pathogenic | 0.9619 | pathogenic | -2.738 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/D | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -4.15 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| I/E | 0.9982 | likely_pathogenic | 0.9981 | pathogenic | -3.876 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| I/F | 0.8167 | likely_pathogenic | 0.7975 | pathogenic | -2.155 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| I/G | 0.9957 | likely_pathogenic | 0.9951 | pathogenic | -3.888 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| I/H | 0.998 | likely_pathogenic | 0.9979 | pathogenic | -3.345 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| I/K | 0.996 | likely_pathogenic | 0.9955 | pathogenic | -3.028 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | N | 0.508914556 | None | None | N |
| I/L | 0.4717 | ambiguous | 0.4492 | ambiguous | -1.805 | Destabilizing | 0.993 | D | 0.343 | neutral | N | 0.502205414 | None | None | N |
| I/M | 0.6047 | likely_pathogenic | 0.5666 | pathogenic | -1.875 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.485530382 | None | None | N |
| I/N | 0.9883 | likely_pathogenic | 0.9881 | pathogenic | -3.629 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| I/P | 0.9971 | likely_pathogenic | 0.9969 | pathogenic | -2.324 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| I/Q | 0.9968 | likely_pathogenic | 0.9964 | pathogenic | -3.403 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| I/R | 0.9941 | likely_pathogenic | 0.9937 | pathogenic | -2.696 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.508914556 | None | None | N |
| I/S | 0.9853 | likely_pathogenic | 0.984 | pathogenic | -4.15 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/T | 0.977 | likely_pathogenic | 0.9739 | pathogenic | -3.75 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.479035922 | None | None | N |
| I/V | 0.1546 | likely_benign | 0.1414 | benign | -2.324 | Highly Destabilizing | 0.993 | D | 0.375 | neutral | N | 0.355363902 | None | None | N |
| I/W | 0.9978 | likely_pathogenic | 0.9975 | pathogenic | -2.56 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Y | 0.9853 | likely_pathogenic | 0.9845 | pathogenic | -2.451 | Highly Destabilizing | 1.0 | D | 0.795 | 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.