Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25229 | 75910;75911;75912 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| N2AB | 23588 | 70987;70988;70989 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| N2A | 22661 | 68206;68207;68208 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| N2B | 16164 | 48715;48716;48717 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| Novex-1 | 16289 | 49090;49091;49092 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| Novex-2 | 16356 | 49291;49292;49293 | chr2:178570447;178570446;178570445 | chr2:179435174;179435173;179435172 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs749230632  |
-2.199 | 1.0 | D | 0.808 | 0.641 | 0.478068462777 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| P/A | rs749230632 |
-2.199 | 1.0 | D | 0.808 | 0.641 | 0.478068462777 | gnomAD-4.0.0 | 4.1066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39759E-06 | 0 | 0 |
| P/L | None | None | 1.0 | D | 0.875 | 0.664 | 0.585836789056 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs749230632 |
None | 1.0 | N | 0.817 | 0.544 | 0.442775082573 | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7992E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.7507 | likely_pathogenic | 0.8088 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.808 | deleterious | D | 0.525870404 | None | None | N |
| P/C | 0.9644 | likely_pathogenic | 0.9775 | pathogenic | -1.285 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/D | 0.9984 | likely_pathogenic | 0.9991 | pathogenic | -2.542 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| P/E | 0.9955 | likely_pathogenic | 0.9976 | pathogenic | -2.433 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| P/F | 0.9983 | likely_pathogenic | 0.999 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| P/G | 0.986 | likely_pathogenic | 0.9907 | pathogenic | -2.417 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| P/H | 0.9919 | likely_pathogenic | 0.995 | pathogenic | -2.216 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| P/I | 0.9722 | likely_pathogenic | 0.9811 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/K | 0.9975 | likely_pathogenic | 0.9985 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| P/L | 0.9249 | likely_pathogenic | 0.9423 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.54996214 | None | None | N |
| P/M | 0.9888 | likely_pathogenic | 0.9927 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| P/N | 0.9967 | likely_pathogenic | 0.9983 | pathogenic | -1.81 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/Q | 0.9903 | likely_pathogenic | 0.9941 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.551736566 | None | None | N |
| P/R | 0.9898 | likely_pathogenic | 0.9936 | pathogenic | -1.423 | Destabilizing | 1.0 | D | 0.874 | deleterious | D | 0.523339189 | None | None | N |
| P/S | 0.9454 | likely_pathogenic | 0.9651 | pathogenic | -2.305 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.503398056 | None | None | N |
| P/T | 0.9325 | likely_pathogenic | 0.9558 | pathogenic | -2.083 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.535834357 | None | None | N |
| P/V | 0.9137 | likely_pathogenic | 0.9346 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| P/W | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.802 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| P/Y | 0.9984 | likely_pathogenic | 0.9992 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.878 | 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.