Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31729 | 95410;95411;95412 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| N2AB | 30088 | 90487;90488;90489 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| N2A | 29161 | 87706;87707;87708 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| N2B | 22664 | 68215;68216;68217 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| Novex-1 | 22789 | 68590;68591;68592 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| Novex-2 | 22856 | 68791;68792;68793 | chr2:178546051;178546050;178546049 | chr2:179410778;179410777;179410776 |
| 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/C | rs869320742  |
-1.772 | 1.0 | D | 0.865 | 0.956 | 0.905035043352 |
Palmio (2013)
Hedberg (2014)
Bugiardini (2018)
Palmio (2019)
| None |
HMERF 
|
het | None | None | N | WES/WGS prioritisation in 12 HMERF families; dominant effect, full penetrance (n = 2, 2 affected (total 4)); Genetic analysis of genes in 12 HMERF families (n = 4, 4 affected) | None | None | None | None | None | None | None | None | None | None | None |
| W/C | rs869320742 |
-1.772 | 1.0 | D | 0.865 | 0.956 | 0.905035043352 | gnomAD-4.0.0 | 6.1583E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09561E-06 | 0 | 0 |
| W/L | rs786205367 |
-2.41 | 1.0 | D | 0.851 | 0.903 | 0.947208517384 |
Izumi (2013)
| None |
MFM
HMERF
|
het | None | None | N | Genetic analysis of single JP family; co-segregates within family (n = 5, 5 affected (total 10)); linkage analysis; not found in ethnic controls | None | None | None | None | None | None | None | None | None | None | None |
| W/R | rs869320741 |
-2.066 | 1.0 | D | 0.917 | 0.934 | 0.922935033018 |
Palmio (2013)
Hedberg (2014)
Huang (2021)
| None |
HMERF
|
het | None | None | N | WES/WGS prioritisation in 12 HMERF families; dominant effect, unknown penetrance | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9902 | likely_pathogenic | 0.9907 | pathogenic | -3.07 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| W/C | 0.9937 | likely_pathogenic | 0.9945 | pathogenic | -2.137 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.690866165 | None | None | N |
| W/D | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.041 | Highly Destabilizing | 1.0 | D | 0.918 | deleterious | None | None | None | None | N |
| W/E | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.909 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| W/F | 0.5515 | ambiguous | 0.5855 | pathogenic | -1.895 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| W/G | 0.9731 | likely_pathogenic | 0.9735 | pathogenic | -3.334 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.690866165 | None | None | N |
| W/H | 0.9951 | likely_pathogenic | 0.9952 | pathogenic | -2.32 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| W/I | 0.9824 | likely_pathogenic | 0.9867 | pathogenic | -2.078 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| W/K | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -2.565 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| W/L | 0.9589 | likely_pathogenic | 0.9639 | pathogenic | -2.078 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.689857143 | None | None | N |
| W/M | 0.9898 | likely_pathogenic | 0.9921 | pathogenic | -1.772 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| W/N | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -3.248 | Highly Destabilizing | 1.0 | D | 0.931 | deleterious | None | None | None | None | N |
| W/P | 0.9987 | likely_pathogenic | 0.9986 | pathogenic | -2.438 | Highly Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| W/Q | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -3.031 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| W/R | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.347 | Highly Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.690866165 | None | None | N |
| W/S | 0.9901 | likely_pathogenic | 0.9905 | pathogenic | -3.509 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | D | 0.690866165 | None | None | N |
| W/T | 0.9948 | likely_pathogenic | 0.9957 | pathogenic | -3.305 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| W/V | 0.9769 | likely_pathogenic | 0.9818 | pathogenic | -2.438 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| W/Y | 0.9019 | likely_pathogenic | 0.915 | pathogenic | -1.741 | Destabilizing | 1.0 | D | 0.859 | 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.