Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19288 | 58087;58088;58089 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| N2AB | 17647 | 53164;53165;53166 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| N2A | 16720 | 50383;50384;50385 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| N2B | 10223 | 30892;30893;30894 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| Novex-1 | 10348 | 31267;31268;31269 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| Novex-2 | 10415 | 31468;31469;31470 | chr2:178594632;178594631;178594630 | chr2:179459359;179459358;179459357 |
| 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 | rs1490097960  |
-2.597 | 1.0 | D | 0.822 | 0.643 | 0.655153318392 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| P/A | rs1490097960 |
-2.597 | 1.0 | D | 0.822 | 0.643 | 0.655153318392 | gnomAD-4.0.0 | 1.60208E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87848E-06 | 0 | 0 |
| P/R | None | None | 1.0 | D | 0.941 | 0.667 | 0.874349025643 |
Huang (2021)
| None |
Other 
|
comp het with K4230Nfs*17 | None | None | N | Genetic analysis of NMD patients; variant prioritisation; no validation | None | None | None | None | None | None | None | None | None | None | None |
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 | 0.9475 | likely_pathogenic | 0.9332 | pathogenic | -2.439 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.591637238 | None | None | N |
| P/C | 0.9922 | likely_pathogenic | 0.9909 | pathogenic | -2.266 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| P/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.384 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| P/E | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -3.123 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/F | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -1.176 | Destabilizing | 1.0 | D | 0.93 | deleterious | None | None | None | None | N |
| P/G | 0.9975 | likely_pathogenic | 0.9968 | pathogenic | -2.973 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/H | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -2.597 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | D | 0.650051649 | None | None | N |
| P/I | 0.964 | likely_pathogenic | 0.9565 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.937 | deleterious | None | None | None | None | N |
| P/K | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -1.889 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| P/L | 0.9679 | likely_pathogenic | 0.9637 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.624109929 | None | None | N |
| P/M | 0.9932 | likely_pathogenic | 0.9927 | pathogenic | -1.384 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/N | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -2.42 | Highly Destabilizing | 1.0 | D | 0.939 | deleterious | None | None | None | None | N |
| P/Q | 0.9986 | likely_pathogenic | 0.9983 | pathogenic | -2.17 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| P/R | 0.9984 | likely_pathogenic | 0.9981 | pathogenic | -1.813 | Destabilizing | 1.0 | D | 0.941 | deleterious | D | 0.649849845 | None | None | N |
| P/S | 0.9964 | likely_pathogenic | 0.9952 | pathogenic | -2.948 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | D | 0.63362868 | None | None | N |
| P/T | 0.9794 | likely_pathogenic | 0.9771 | pathogenic | -2.55 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.649849845 | None | None | N |
| P/V | 0.8915 | likely_pathogenic | 0.879 | pathogenic | -1.397 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| P/W | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -1.689 | Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| P/Y | 0.9999 | likely_pathogenic | 0.9998 | pathogenic | -1.452 | Destabilizing | 1.0 | D | 0.932 | 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.