Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27247 | 81964;81965;81966 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| N2AB | 25606 | 77041;77042;77043 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| N2A | 24679 | 74260;74261;74262 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| N2B | 18182 | 54769;54770;54771 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| Novex-1 | 18307 | 55144;55145;55146 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| Novex-2 | 18374 | 55345;55346;55347 | chr2:178564393;178564392;178564391 | chr2:179429120;179429119;179429118 |
| 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/E | None | None | 1.0 | D | 0.827 | 0.547 | 0.823787080964 | gnomAD-4.0.0 | 6.84298E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99481E-07 | 0 | 0 |
| A/V | rs374380013  |
-1.087 | 1.0 | D | 0.69 | 0.571 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/V | rs374380013 |
-1.087 | 1.0 | D | 0.69 | 0.571 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs374380013 |
-1.087 | 1.0 | D | 0.69 | 0.571 | None | gnomAD-4.0.0 | 1.23959E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69526E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.852 | likely_pathogenic | 0.8324 | pathogenic | -1.497 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/D | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -2.666 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| A/E | 0.9978 | likely_pathogenic | 0.9978 | pathogenic | -2.403 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.580042854 | None | None | N |
| A/F | 0.9947 | likely_pathogenic | 0.994 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| A/G | 0.6447 | likely_pathogenic | 0.6261 | pathogenic | -1.953 | Destabilizing | 1.0 | D | 0.623 | neutral | D | 0.541174545 | None | None | N |
| A/H | 0.9987 | likely_pathogenic | 0.9987 | pathogenic | -2.223 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/I | 0.982 | likely_pathogenic | 0.9786 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| A/K | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/L | 0.9279 | likely_pathogenic | 0.9177 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| A/M | 0.978 | likely_pathogenic | 0.9719 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/N | 0.997 | likely_pathogenic | 0.9966 | pathogenic | -1.686 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| A/P | 0.9952 | likely_pathogenic | 0.9948 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.568940038 | None | None | N |
| A/Q | 0.994 | likely_pathogenic | 0.994 | pathogenic | -1.364 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| A/R | 0.997 | likely_pathogenic | 0.9974 | pathogenic | -1.421 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| A/S | 0.4061 | ambiguous | 0.3871 | ambiguous | -2.076 | Highly Destabilizing | 1.0 | D | 0.613 | neutral | N | 0.516763186 | None | None | N |
| A/T | 0.8501 | likely_pathogenic | 0.8156 | pathogenic | -1.678 | Destabilizing | 1.0 | D | 0.778 | deleterious | D | 0.564884206 | None | None | N |
| A/V | 0.8994 | likely_pathogenic | 0.8843 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | D | 0.546085616 | None | None | N |
| A/W | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.456 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| A/Y | 0.9983 | likely_pathogenic | 0.9982 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.866 | 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.