Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16521 | 49786;49787;49788 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| N2AB | 14880 | 44863;44864;44865 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| N2A | 13953 | 42082;42083;42084 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| N2B | 7456 | 22591;22592;22593 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| Novex-1 | 7581 | 22966;22967;22968 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| Novex-2 | 7648 | 23167;23168;23169 | chr2:178613248;178613247;178613246 | chr2:179477975;179477974;179477973 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs758275324  |
-2.797 | 1.0 | D | 0.847 | 0.856 | 0.729213996001 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| Y/H | rs758275324 |
-2.797 | 1.0 | D | 0.847 | 0.856 | 0.729213996001 | gnomAD-4.0.0 | 2.05678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70103E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9975 | likely_pathogenic | 0.9958 | pathogenic | -2.947 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/C | 0.9696 | likely_pathogenic | 0.9424 | pathogenic | -1.697 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.801164182 | None | None | N |
| Y/D | 0.9973 | likely_pathogenic | 0.9965 | pathogenic | -3.543 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.801164182 | None | None | N |
| Y/E | 0.9989 | likely_pathogenic | 0.9983 | pathogenic | -3.319 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| Y/F | 0.3857 | ambiguous | 0.3197 | benign | -1.027 | Destabilizing | 0.999 | D | 0.74 | deleterious | D | 0.680618578 | None | None | N |
| Y/G | 0.9921 | likely_pathogenic | 0.9879 | pathogenic | -3.375 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| Y/H | 0.9806 | likely_pathogenic | 0.9624 | pathogenic | -2.108 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.801164182 | None | None | N |
| Y/I | 0.9834 | likely_pathogenic | 0.9767 | pathogenic | -1.518 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| Y/K | 0.9992 | likely_pathogenic | 0.9988 | pathogenic | -2.32 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| Y/L | 0.9653 | likely_pathogenic | 0.9554 | pathogenic | -1.518 | Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| Y/M | 0.9894 | likely_pathogenic | 0.9842 | pathogenic | -1.25 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| Y/N | 0.9804 | likely_pathogenic | 0.9713 | pathogenic | -3.209 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | D | 0.801474134 | None | None | N |
| Y/P | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -2.012 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| Y/Q | 0.9983 | likely_pathogenic | 0.9968 | pathogenic | -2.893 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| Y/R | 0.9977 | likely_pathogenic | 0.9962 | pathogenic | -2.211 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| Y/S | 0.9923 | likely_pathogenic | 0.9881 | pathogenic | -3.501 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | D | 0.801164182 | None | None | N |
| Y/T | 0.9969 | likely_pathogenic | 0.9954 | pathogenic | -3.151 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| Y/V | 0.9688 | likely_pathogenic | 0.9557 | pathogenic | -2.012 | Highly Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| Y/W | 0.8999 | likely_pathogenic | 0.8687 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.825 | 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.