Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15979 | 48160;48161;48162 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| N2AB | 14338 | 43237;43238;43239 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| N2A | 13411 | 40456;40457;40458 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| N2B | 6914 | 20965;20966;20967 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| Novex-1 | 7039 | 21340;21341;21342 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| Novex-2 | 7106 | 21541;21542;21543 | chr2:178616954;178616953;178616952 | chr2:179481681;179481680;179481679 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs184815126  |
-0.313 | 1.0 | N | 0.766 | 0.406 | None | gnomAD-2.1.1 | 8.96E-05 | None | None | None | None | N | None | 0 | 1.41547E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.49336E-04 | 1.40885E-04 |
| P/L | rs184815126 |
-0.313 | 1.0 | N | 0.766 | 0.406 | None | gnomAD-3.1.2 | 1.44859E-04 | None | None | None | None | N | None | 2.41E-05 | 1.9698E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.65088E-04 | 0 | 0 |
| P/L | rs184815126 |
-0.313 | 1.0 | N | 0.766 | 0.406 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/L | rs184815126 |
-0.313 | 1.0 | N | 0.766 | 0.406 | None | gnomAD-4.0.0 | 1.19057E-04 | None | None | None | None | N | None | 1.33461E-05 | 1.5016E-04 | None | 0 | 4.47227E-05 | None | 0 | 1.65344E-04 | 1.41633E-04 | 0 | 1.92252E-04 |
| P/S | rs1473380697 |
-0.475 | 1.0 | N | 0.765 | 0.339 | 0.266843984389 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1473380697 |
-0.475 | 1.0 | N | 0.765 | 0.339 | 0.266843984389 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1473380697 |
-0.475 | 1.0 | N | 0.765 | 0.339 | 0.266843984389 | gnomAD-4.0.0 | 6.58458E-06 | None | None | None | None | N | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1092 | likely_benign | 0.1182 | benign | -1.054 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.450438219 | None | None | N |
| P/C | 0.6638 | likely_pathogenic | 0.6642 | pathogenic | -0.843 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/D | 0.5257 | ambiguous | 0.5739 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| P/E | 0.3746 | ambiguous | 0.418 | ambiguous | -0.713 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| P/F | 0.815 | likely_pathogenic | 0.8312 | pathogenic | -1.111 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/G | 0.4783 | ambiguous | 0.4914 | ambiguous | -1.264 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/H | 0.349 | ambiguous | 0.3704 | ambiguous | -0.771 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.46907102 | None | None | N |
| P/I | 0.6048 | likely_pathogenic | 0.6388 | pathogenic | -0.62 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| P/K | 0.4218 | ambiguous | 0.4281 | ambiguous | -0.712 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| P/L | 0.3209 | likely_benign | 0.351 | ambiguous | -0.62 | Destabilizing | 1.0 | D | 0.766 | deleterious | N | 0.467502048 | None | None | N |
| P/M | 0.5859 | likely_pathogenic | 0.6128 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| P/N | 0.497 | ambiguous | 0.524 | ambiguous | -0.44 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| P/Q | 0.2669 | likely_benign | 0.2856 | benign | -0.715 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| P/R | 0.2812 | likely_benign | 0.288 | benign | -0.172 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.46516783 | None | None | N |
| P/S | 0.1929 | likely_benign | 0.209 | benign | -0.941 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.43173736 | None | None | N |
| P/T | 0.1788 | likely_benign | 0.1934 | benign | -0.915 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.44549043 | None | None | N |
| P/V | 0.3983 | ambiguous | 0.4264 | ambiguous | -0.729 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| P/W | 0.8887 | likely_pathogenic | 0.8986 | pathogenic | -1.166 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7382 | likely_pathogenic | 0.7649 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.741 | 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.