Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19358 | 58297;58298;58299 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| N2AB | 17717 | 53374;53375;53376 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| N2A | 16790 | 50593;50594;50595 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| N2B | 10293 | 31102;31103;31104 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| Novex-1 | 10418 | 31477;31478;31479 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| Novex-2 | 10485 | 31678;31679;31680 | chr2:178594422;178594421;178594420 | chr2:179459149;179459148;179459147 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs371973579  |
-1.915 | 1.0 | D | 0.865 | 0.553 | None | gnomAD-2.1.1 | 1.14861E-04 | None | None | None | None | N | None | 7.03293E-04 | 0 | None | 0 | 7.74954E-04 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs371973579 |
-1.915 | 1.0 | D | 0.865 | 0.553 | None | gnomAD-3.1.2 | 1.90737E-04 | None | None | None | None | N | None | 5.55421E-04 | 0 | 0 | 0 | 9.69368E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs371973579 |
-1.915 | 1.0 | D | 0.865 | 0.553 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs371973579 |
-1.915 | 1.0 | D | 0.865 | 0.553 | None | gnomAD-4.0.0 | 4.71491E-05 | None | None | None | None | N | None | 6.53961E-04 | 0 | None | 0 | 4.24961E-04 | None | 0 | 0 | 4.24139E-06 | 0 | 4.80754E-05 |
| R/H | rs1023184567 |
-2.648 | 1.0 | D | 0.812 | 0.519 | 0.580541342914 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 6.63E-05 | None | 0 | 0 | 0 |
| R/H | rs1023184567 |
-2.648 | 1.0 | D | 0.812 | 0.519 | 0.580541342914 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 9.49367E-03 | 1.47E-05 | 0 | 0 |
| R/H | rs1023184567 |
-2.648 | 1.0 | D | 0.812 | 0.519 | 0.580541342914 | gnomAD-4.0.0 | 2.54385E-05 | None | None | None | None | N | None | 5.33703E-05 | 1.67151E-05 | None | 0 | 4.47187E-05 | None | 0 | 4.95868E-04 | 2.12088E-05 | 3.30812E-05 | 4.80908E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9931 | likely_pathogenic | 0.9943 | pathogenic | -1.993 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/C | 0.8519 | likely_pathogenic | 0.8712 | pathogenic | -2.087 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.533993797 | None | None | N |
| R/D | 0.999 | likely_pathogenic | 0.9991 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| R/E | 0.9855 | likely_pathogenic | 0.9858 | pathogenic | -0.709 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| R/F | 0.9935 | likely_pathogenic | 0.9942 | pathogenic | -1.518 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| R/G | 0.9934 | likely_pathogenic | 0.9942 | pathogenic | -2.305 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | D | 0.551844563 | None | None | N |
| R/H | 0.7309 | likely_pathogenic | 0.7286 | pathogenic | -2.202 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | D | 0.533993797 | None | None | N |
| R/I | 0.9754 | likely_pathogenic | 0.9784 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| R/K | 0.7248 | likely_pathogenic | 0.7109 | pathogenic | -1.68 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | N |
| R/L | 0.9726 | likely_pathogenic | 0.978 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.514243701 | None | None | N |
| R/M | 0.9837 | likely_pathogenic | 0.9865 | pathogenic | -1.52 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/N | 0.9961 | likely_pathogenic | 0.9965 | pathogenic | -1.358 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.388 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.552351542 | None | None | N |
| R/Q | 0.7091 | likely_pathogenic | 0.708 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/S | 0.9954 | likely_pathogenic | 0.9959 | pathogenic | -2.312 | Highly Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.505098987 | None | None | N |
| R/T | 0.9907 | likely_pathogenic | 0.9924 | pathogenic | -1.937 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| R/V | 0.977 | likely_pathogenic | 0.981 | pathogenic | -1.388 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/W | 0.9345 | likely_pathogenic | 0.9371 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| R/Y | 0.9811 | likely_pathogenic | 0.9813 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.872 | 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.