Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20236 | 60931;60932;60933 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| N2AB | 18595 | 56008;56009;56010 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| N2A | 17668 | 53227;53228;53229 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| N2B | 11171 | 33736;33737;33738 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| Novex-1 | 11296 | 34111;34112;34113 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| Novex-2 | 11363 | 34312;34313;34314 | chr2:178591019;178591018;178591017 | chr2:179455746;179455745;179455744 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/R | rs778953994  |
-2.024 | 1.0 | D | 0.851 | 0.885 | 0.930790671375 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| L/R | rs778953994 |
-2.024 | 1.0 | D | 0.851 | 0.885 | 0.930790671375 | 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 |
| L/R | rs778953994 |
-2.024 | 1.0 | D | 0.851 | 0.885 | 0.930790671375 | gnomAD-4.0.0 | 6.57592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9793 | likely_pathogenic | 0.9824 | pathogenic | -2.644 | Highly Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| L/C | 0.9601 | likely_pathogenic | 0.9638 | pathogenic | -1.968 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.403 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/E | 0.9973 | likely_pathogenic | 0.9975 | pathogenic | -3.233 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/F | 0.8448 | likely_pathogenic | 0.8362 | pathogenic | -1.65 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/G | 0.9944 | likely_pathogenic | 0.9946 | pathogenic | -3.125 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/H | 0.989 | likely_pathogenic | 0.9897 | pathogenic | -2.701 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/I | 0.3645 | ambiguous | 0.396 | ambiguous | -1.258 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| L/K | 0.9905 | likely_pathogenic | 0.9897 | pathogenic | -2.197 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/M | 0.5946 | likely_pathogenic | 0.604 | pathogenic | -1.082 | Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.59950581 | None | None | N |
| L/N | 0.9959 | likely_pathogenic | 0.9961 | pathogenic | -2.449 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| L/P | 0.9898 | likely_pathogenic | 0.9897 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.854 | deleterious | D | 0.663229648 | None | None | N |
| L/Q | 0.9827 | likely_pathogenic | 0.9845 | pathogenic | -2.385 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.646978122 | None | None | N |
| L/R | 0.9766 | likely_pathogenic | 0.9765 | pathogenic | -1.768 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.663229648 | None | None | N |
| L/S | 0.9954 | likely_pathogenic | 0.9963 | pathogenic | -3.001 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| L/T | 0.9778 | likely_pathogenic | 0.9814 | pathogenic | -2.713 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| L/V | 0.5357 | ambiguous | 0.5778 | pathogenic | -1.703 | Destabilizing | 0.999 | D | 0.837 | deleterious | D | 0.589320926 | None | None | N |
| L/W | 0.9816 | likely_pathogenic | 0.9812 | pathogenic | -2.161 | Highly Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| L/Y | 0.9887 | likely_pathogenic | 0.9879 | pathogenic | -1.929 | Destabilizing | 1.0 | D | 0.829 | 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.