Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15954 | 48085;48086;48087 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| N2AB | 14313 | 43162;43163;43164 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| N2A | 13386 | 40381;40382;40383 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| N2B | 6889 | 20890;20891;20892 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| Novex-1 | 7014 | 21265;21266;21267 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| Novex-2 | 7081 | 21466;21467;21468 | chr2:178617135;178617134;178617133 | chr2:179481862;179481861;179481860 |
| 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/T | rs377037421  |
-2.058 | 1.0 | D | 0.755 | 0.264 | None | gnomAD-2.1.1 | 7E-05 | None | None | None | None | N | None | 6.64E-05 | 2.96E-05 | None | 1.00888E-04 | 0 | None | 3.31E-05 | None | 4.68E-05 | 1.00626E-04 | 1.69377E-04 |
| A/T | rs377037421 |
-2.058 | 1.0 | D | 0.755 | 0.264 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | N | None | 1.2079E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| A/T | rs377037421 |
-2.058 | 1.0 | D | 0.755 | 0.264 | None | gnomAD-4.0.0 | 5.53064E-05 | None | None | None | None | N | None | 1.47236E-04 | 3.36417E-05 | None | 3.38937E-05 | 2.25215E-05 | None | 6.26802E-05 | 0 | 4.9251E-05 | 2.21082E-05 | 1.60637E-04 |
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 | 0.5758 | likely_pathogenic | 0.615 | pathogenic | -1.933 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| A/D | 0.9596 | likely_pathogenic | 0.9725 | pathogenic | -3.105 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | D | 0.576553777 | None | None | N |
| A/E | 0.9234 | likely_pathogenic | 0.9427 | pathogenic | -3.056 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/F | 0.8686 | likely_pathogenic | 0.9087 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.738 | deleterious | None | None | None | None | N |
| A/G | 0.391 | ambiguous | 0.432 | ambiguous | -1.057 | Destabilizing | 0.999 | D | 0.57 | neutral | D | 0.634878798 | None | None | N |
| A/H | 0.9684 | likely_pathogenic | 0.9783 | pathogenic | -0.986 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| A/I | 0.4833 | ambiguous | 0.5528 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| A/K | 0.973 | likely_pathogenic | 0.9791 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/L | 0.5155 | ambiguous | 0.5637 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| A/M | 0.5711 | likely_pathogenic | 0.6176 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| A/N | 0.8836 | likely_pathogenic | 0.908 | pathogenic | -1.661 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| A/P | 0.4954 | ambiguous | 0.536 | ambiguous | -0.403 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.500915826 | None | None | N |
| A/Q | 0.9133 | likely_pathogenic | 0.9287 | pathogenic | -1.82 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| A/R | 0.9338 | likely_pathogenic | 0.9489 | pathogenic | -0.99 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/S | 0.2218 | likely_benign | 0.2515 | benign | -1.816 | Destabilizing | 1.0 | D | 0.613 | neutral | D | 0.634878798 | None | None | N |
| A/T | 0.2123 | likely_benign | 0.2611 | benign | -1.691 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.542325949 | None | None | N |
| A/V | 0.1979 | likely_benign | 0.2493 | benign | -0.403 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | N | 0.45037515 | None | None | N |
| A/W | 0.9851 | likely_pathogenic | 0.9899 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| A/Y | 0.9564 | likely_pathogenic | 0.9696 | pathogenic | -0.938 | Destabilizing | 1.0 | D | 0.774 | 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.