Dilated Cardiomyopathy

Gene: DSG2

I don't know

Assessed as LIMITED by ClinGen for mono-allelic variants:

Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship.

Bi-allelic variants: three families reported, two with missense variants.

DEFINITIVE for ARVC.

Created: 12 Aug 2022, 12:24 a.m. | Last Modified: 12 Aug 2022, 12:26 a.m.

Panel Version: 1.9

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cardiomyopathy, dilated, 1BB, MIM# 612877

Publications

• 33949662
• 18678517
• 21859740
• 28764973
• 35941102

Green List (high evidence)

- ARVD/C: Autosomal dominance with reduced penetrance is the usual reported inheritance. Digenic inheritance has also been reported (OMIM)

- Cardiomyopathy, dilated: The text in OMIM suggests both autosomal recessive and autosomal dominance, with the recessive being more severe. Note: the term digenic inheritance may be preferable, as in the comment above for ARVD/C.

- Many LoF variants reported. Missense variants presumed to be LoF, however functional studies of the p.R46Q variant in transfected cells demonstrated increased binding, consistent with a GoF effect (PMID: 23071725).

Created: 27 Feb 2020, 11:20 p.m. | Last Modified: 27 Feb 2020, 11:20 p.m.

Panel Version: 0.11

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Arrhythmogenic right ventricular dysplasia, 10, 610193; Cardiomyopathy, dilated, 1BB, 612877

Publications

• 23071725