Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28498 | 85717;85718;85719 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| N2AB | 26857 | 80794;80795;80796 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| N2A | 25930 | 78013;78014;78015 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| N2B | 19433 | 58522;58523;58524 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| Novex-1 | 19558 | 58897;58898;58899 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| Novex-2 | 19625 | 59098;59099;59100 | chr2:178560640;178560639;178560638 | chr2:179425367;179425366;179425365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | rs1488730809  |
-0.952 | 1.0 | D | 0.781 | 0.645 | 0.765773251811 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| W/R | rs1488730809 |
-0.952 | 1.0 | D | 0.781 | 0.645 | 0.765773251811 | gnomAD-4.0.0 | 2.05285E-06 | None | None | None | None | I | None | 0 | 2.23654E-05 | None | 0 | 0 | None | 0 | 0 | 1.79893E-06 | 0 | 0 |
| W/S | rs756499458 |
-2.162 | 1.0 | D | 0.789 | 0.576 | 0.876021886608 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9717 | likely_pathogenic | 0.9835 | pathogenic | -2.942 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| W/C | 0.9916 | likely_pathogenic | 0.9954 | pathogenic | -1.188 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.522363414 | None | None | I |
| W/D | 0.9932 | likely_pathogenic | 0.9967 | pathogenic | -1.377 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| W/E | 0.9937 | likely_pathogenic | 0.9968 | pathogenic | -1.317 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| W/F | 0.6978 | likely_pathogenic | 0.742 | pathogenic | -1.898 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| W/G | 0.9171 | likely_pathogenic | 0.9473 | pathogenic | -3.126 | Highly Destabilizing | 1.0 | D | 0.683 | prob.neutral | D | 0.5397072 | None | None | I |
| W/H | 0.9857 | likely_pathogenic | 0.9919 | pathogenic | -1.385 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| W/I | 0.9792 | likely_pathogenic | 0.9895 | pathogenic | -2.286 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| W/K | 0.9961 | likely_pathogenic | 0.9982 | pathogenic | -1.317 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | I |
| W/L | 0.9274 | likely_pathogenic | 0.9569 | pathogenic | -2.286 | Highly Destabilizing | 1.0 | D | 0.683 | prob.neutral | D | 0.537679284 | None | None | I |
| W/M | 0.9816 | likely_pathogenic | 0.9895 | pathogenic | -1.725 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| W/N | 0.9891 | likely_pathogenic | 0.9951 | pathogenic | -1.548 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| W/P | 0.9843 | likely_pathogenic | 0.9916 | pathogenic | -2.518 | Highly Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| W/Q | 0.9963 | likely_pathogenic | 0.9981 | pathogenic | -1.622 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| W/R | 0.9929 | likely_pathogenic | 0.9963 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.781 | deleterious | D | 0.550810016 | None | None | I |
| W/S | 0.9293 | likely_pathogenic | 0.9596 | pathogenic | -2.065 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.538946731 | None | None | I |
| W/T | 0.9697 | likely_pathogenic | 0.9855 | pathogenic | -1.96 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| W/V | 0.9654 | likely_pathogenic | 0.9817 | pathogenic | -2.518 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| W/Y | 0.8729 | likely_pathogenic | 0.906 | pathogenic | -1.645 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
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.