Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3214 | 9865;9866;9867 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| N2AB | 3214 | 9865;9866;9867 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| N2A | 3214 | 9865;9866;9867 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| N2B | 3168 | 9727;9728;9729 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| Novex-1 | 3168 | 9727;9728;9729 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| Novex-2 | 3168 | 9727;9728;9729 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
| Novex-3 | 3214 | 9865;9866;9867 | chr2:178766444;178766443;178766442 | chr2:179631171;179631170;179631169 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs368323634  |
-0.632 | 1.0 | D | 0.585 | 0.63 | 0.512942373286 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| D/E | rs368323634 |
-0.632 | 1.0 | D | 0.585 | 0.63 | 0.512942373286 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs368323634 |
-0.632 | 1.0 | D | 0.585 | 0.63 | 0.512942373286 | gnomAD-4.0.0 | 1.05323E-05 | None | None | None | None | N | None | 0 | 1.66661E-05 | None | 0 | 0 | None | 0 | 0 | 1.27116E-05 | 0 | 1.60041E-05 |
| D/N | rs778326573 |
-0.939 | 1.0 | D | 0.805 | 0.757 | 0.63923631105 | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.33E-05 | 1.38581E-04 |
| D/N | rs778326573 |
-0.939 | 1.0 | D | 0.805 | 0.757 | 0.63923631105 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.77555E-04 |
| D/N | rs778326573 |
-0.939 | 1.0 | D | 0.805 | 0.757 | 0.63923631105 | gnomAD-4.0.0 | 6.19574E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.77962E-06 | 1.09791E-05 | 1.60036E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9902 | likely_pathogenic | 0.9955 | pathogenic | 0.005 | Stabilizing | 1.0 | D | 0.866 | deleterious | D | 0.697197131 | None | None | N |
| D/C | 0.9977 | likely_pathogenic | 0.9988 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| D/E | 0.966 | likely_pathogenic | 0.9782 | pathogenic | -0.951 | Destabilizing | 1.0 | D | 0.585 | neutral | D | 0.698190486 | None | None | N |
| D/F | 0.9985 | likely_pathogenic | 0.9994 | pathogenic | 0.545 | Stabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| D/G | 0.9945 | likely_pathogenic | 0.9972 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.696469704 | None | None | N |
| D/H | 0.9877 | likely_pathogenic | 0.9947 | pathogenic | 0.037 | Stabilizing | 1.0 | D | 0.873 | deleterious | D | 0.696560552 | None | None | N |
| D/I | 0.9987 | likely_pathogenic | 0.9995 | pathogenic | 1.211 | Stabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| D/K | 0.9972 | likely_pathogenic | 0.9988 | pathogenic | -0.445 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| D/L | 0.9974 | likely_pathogenic | 0.9988 | pathogenic | 1.211 | Stabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| D/M | 0.9993 | likely_pathogenic | 0.9997 | pathogenic | 1.689 | Stabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| D/N | 0.9621 | likely_pathogenic | 0.9811 | pathogenic | -1.087 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.698590967 | None | None | N |
| D/P | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | 0.838 | Stabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| D/Q | 0.996 | likely_pathogenic | 0.998 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| D/R | 0.9968 | likely_pathogenic | 0.9984 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| D/S | 0.9807 | likely_pathogenic | 0.9915 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| D/T | 0.9963 | likely_pathogenic | 0.9983 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| D/V | 0.994 | likely_pathogenic | 0.9974 | pathogenic | 0.838 | Stabilizing | 1.0 | D | 0.873 | deleterious | D | 0.696492131 | None | None | N |
| D/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | 0.546 | Stabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| D/Y | 0.9886 | likely_pathogenic | 0.9953 | pathogenic | 0.744 | Stabilizing | 1.0 | D | 0.893 | deleterious | D | 0.696560552 | 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.