Case1: 17 month onset

DiseaseAssertion: Noncompaction of the ventricular myocardium

FamilyInfo: No known family history of heart disease or sudden cardiac death, Has two sisters with the same MYH7 variant and similar phenotypes, See Fig 3 for pedigree

CasePresentingHPOs: HP:0001279, HP:0001635, HP:0012818, HP:0031295, HP:0030718, HP:0005133, HP:0005180, HP:0001653, HP:0001723, HP:0002092, HP:0004890, HP:0030876, HP:0005168 (Syncope, Heart failure, Biventricular noncompaction cardiomyopathy, Left atrial enlargement, Right atrial enlargement, Right ventricular dilation, Tricuspid regurgitation, Mitral regurgitation, Restrictive cardiomyopathy, Pulmonary arterial hypertension, Elevated pulmonary artery pressure, Increased pulmonary capillary wedge pressure, Elevated right atrial pressure)

HPOsFreeText: Both cardiac ventricles had a coarsely trabeculated and spongy appearance in posterior wall, lateral wall, apical segments, and right ventricle, LVEF at 51%, Short E-wave deceleration time at the transmitral level (85 msec) with a high E/A ratio (2.1), Ratio between the thickness of the noncompacted layer and the myocardial layer was 3.4:1, Underwent cardiac catheterization, Left ventricular systolic pressure and end-diastolic pressure were 95 mmHg and 37 mmHg respectively, Pulmonary vascular resistance was 4.0 Wood Unit m^2

CaseNotHPOs: N/A

NotHPOsFreeText: Normal left ventricle end-diastolic volume (110%), No other congenital heart disease

CaseAddInfo: Died at age 2 yrs of advanced heart failure

CasePreviousTesting: TruSight One sequencing panel was used for testing (Illumina)

CaseGenotypingMethod: Blood samples were collected from the proband and his siblings and genomic DNA was extracted. Target enrichment was performed using the TruSight One sequencing panel (Illumina). Analysis was annotated and filtered, after which the MYH7 pathogenic variant was confirmed using PCR and Sanger sequencing.

Variant: NM_000257.4(MYH7):c.5740G>A (p.Glu1914Lys)

ClinVar: 43088 https://www.ncbi.nlm.nih.gov/clinvar/variation/43088/

gnomAD: Not in gnomAD

MultipleGeneVariants

(1) PLEC Variant

Variant: NM_000445.4:c.3005-8T>C

CAID: CA187619061 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA187619061

gnomAD: Not in gnomAD