Hypertrophic cardiomyopathy_HCM

Gene: NEXN

Red List (low evidence)

ClinGen curation: Two probands reported in a single 2010 publication (Wang et al, PMID 20970104). Two unique missense variants were reported in this publication. The pathogenicity of one variant was supported by functional studies in a cell culture model system that showed mutant protein fragments accumulated in the cytoplasm and failed to bind to actin filaments. This variant also segregated with disease in 2 additional family members. The second variant reported by Wang et al. was found at a high frequency in the ExAC database, which is consistent with benign variation. The mechanism for disease is unknown. This gene-disease association is supported by a cell culture model system, expression studies and localization of NEXN to the intercalated disk (Hassel et al, 2009, PMID 1988149; Somi et al, 2016, 27148881), and interaction with alpha actin (Wang et al, PMID 20970104).
In summary: one family plus functional data.

Created: 21 Jun 2020, 7:56 a.m. | Last Modified: 21 Jun 2020, 7:56 a.m.

Panel Version: 0.77

Phenotypes
Cardiomyopathy, hypertrophic, 20, MIM# 613876

Publications

• 20970104

Red List (low evidence)

LIMITED evidence by ClinGen HCM working group PMID: 30681346

Created: 21 Jun 2020, 6:35 a.m. | Last Modified: 21 Jun 2020, 6:35 a.m.

Panel Version: 0.67

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
HCM

Publications

• PMID: 30681346