Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27661 | 83206;83207;83208 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| N2AB | 26020 | 78283;78284;78285 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| N2A | 25093 | 75502;75503;75504 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| N2B | 18596 | 56011;56012;56013 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| Novex-1 | 18721 | 56386;56387;56388 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| Novex-2 | 18788 | 56587;56588;56589 | chr2:178563151;178563150;178563149 | chr2:179427878;179427877;179427876 |
| 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 | rs770498921  |
-0.008 | 0.007 | N | 0.626 | 0.325 | 0.520749599713 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.89E-06 | 0 |
| P/L | rs770498921 |
-0.008 | 0.007 | N | 0.626 | 0.325 | 0.520749599713 | gnomAD-4.0.0 | 3.18288E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 3.02499E-05 |
| P/S | rs201422612 |
-0.313 | 0.162 | N | 0.439 | 0.175 | None | gnomAD-2.1.1 | 8.57E-05 | None | None | None | None | N | None | 4.95991E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-05 | 2.80741E-04 |
| P/S | rs201422612 |
-0.313 | 0.162 | N | 0.439 | 0.175 | None | gnomAD-3.1.2 | 1.1832E-04 | None | None | None | None | N | None | 2.89617E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| P/S | rs201422612 |
-0.313 | 0.162 | N | 0.439 | 0.175 | None | gnomAD-4.0.0 | 7.43676E-05 | None | None | None | None | N | None | 4.27282E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 6.69655E-05 | 0 | 1.4412E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0836 | likely_benign | 0.0772 | benign | -0.491 | Destabilizing | 0.307 | N | 0.697 | prob.delet. | N | 0.511118473 | None | None | N |
| P/C | 0.4738 | ambiguous | 0.4419 | ambiguous | -0.988 | Destabilizing | 0.996 | D | 0.785 | deleterious | None | None | None | None | N |
| P/D | 0.4389 | ambiguous | 0.3915 | ambiguous | -0.299 | Destabilizing | 0.909 | D | 0.666 | prob.neutral | None | None | None | None | N |
| P/E | 0.3009 | likely_benign | 0.2651 | benign | -0.395 | Destabilizing | 0.909 | D | 0.684 | prob.delet. | None | None | None | None | N |
| P/F | 0.456 | ambiguous | 0.4329 | ambiguous | -0.751 | Destabilizing | 0.909 | D | 0.799 | deleterious | None | None | None | None | N |
| P/G | 0.2778 | likely_benign | 0.2525 | benign | -0.561 | Destabilizing | 0.74 | D | 0.673 | prob.neutral | None | None | None | None | N |
| P/H | 0.1926 | likely_benign | 0.1784 | benign | -0.072 | Destabilizing | 0.994 | D | 0.775 | deleterious | N | 0.498802926 | None | None | N |
| P/I | 0.2967 | likely_benign | 0.2752 | benign | -0.437 | Destabilizing | 0.833 | D | 0.642 | neutral | None | None | None | None | N |
| P/K | 0.3477 | ambiguous | 0.3096 | benign | -0.516 | Destabilizing | 0.909 | D | 0.691 | prob.delet. | None | None | None | None | N |
| P/L | 0.1182 | likely_benign | 0.1102 | benign | -0.437 | Destabilizing | 0.007 | N | 0.626 | neutral | N | 0.492054977 | None | None | N |
| P/M | 0.2845 | likely_benign | 0.2652 | benign | -0.744 | Destabilizing | 0.974 | D | 0.771 | deleterious | None | None | None | None | N |
| P/N | 0.3019 | likely_benign | 0.2847 | benign | -0.42 | Destabilizing | 0.909 | D | 0.749 | deleterious | None | None | None | None | N |
| P/Q | 0.1598 | likely_benign | 0.1464 | benign | -0.576 | Destabilizing | 0.953 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/R | 0.2481 | likely_benign | 0.2146 | benign | -0.096 | Destabilizing | 0.938 | D | 0.805 | deleterious | N | 0.498295947 | None | None | N |
| P/S | 0.1205 | likely_benign | 0.1109 | benign | -0.755 | Destabilizing | 0.162 | N | 0.439 | neutral | N | 0.47055993 | None | None | N |
| P/T | 0.0958 | likely_benign | 0.088 | benign | -0.754 | Destabilizing | 0.028 | N | 0.473 | neutral | N | 0.47869941 | None | None | N |
| P/V | 0.1995 | likely_benign | 0.1844 | benign | -0.429 | Destabilizing | 0.587 | D | 0.66 | prob.neutral | None | None | None | None | N |
| P/W | 0.6074 | likely_pathogenic | 0.5612 | ambiguous | -0.796 | Destabilizing | 0.996 | D | 0.832 | deleterious | None | None | None | None | N |
| P/Y | 0.4446 | ambiguous | 0.4124 | ambiguous | -0.554 | Destabilizing | 0.953 | D | 0.79 | 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.