Case1: Female, 23 years old, ethnicity not stated

DiseaseAssertion: Hypertrophic cardiomyopathy (HCM)

FamilyInfo: Mother, brother, and sister carry the same MYL2 mutation. Mother has phenotypic HCM without scar or high-risk features for sudden cardiac death. Sister and brother remain phenotypically negative with yearly imaging.

ParentalTesting: Maternal testing confirmed — mother carries the same MYL2 mutation and has phenotypic HCM. Paternal testing not reported.

CasePresentingHPOs: HP:0011675, HP:0001279, HP:0001962, HP:0004756

CaseHPOFreeText: During a sprinting drill, she developed a 42-second episode of polymorphic VT with spontaneous termination. The ambulatory rhythm monitoring showed a ~4% premature ventricular contraction (PVC) burden without sustained or nonsustained VT. CPET 2 demonstrated monomorphic nonsustained VT at peak exertion. Given exercise-induced polymorphic VT, she underwent placement of a subcutaneous implantable cardioverter-defibrillator (ICD) for secondary prevention. In the emergency department, high-sensitivity troponin rose from 105 to 303 ng/L. Cardiac magnetic resonance imaging (MRI) demonstrated normal LV function with subepicardial late gadolinium enhancement (LGE) in the basal to mid inferolateral wall, concerning for acute myocarditis

CaseNotHPOs:HP:0100749, HP:0002094, HP:0031972, HP:0001714

CaseNotHPOFreeText: Normal LV size and function on echocardiography. Normal strain. Repeat cardiac MRI showed complete resolution of LGE. Normal biventricular size, thickness, and function without LGE or scar on third MRI. No sustained VT/VF after ICD placement. Normal complete blood count and basic metabolic panel. Coronary CT angiography unremarkable.

CasePreviousTesting: She underwent coronary computed tomography angiography to rule out ischemia and anomalous coronary origins, which was unremarkable. Cardiac magnetic resonance imaging (MRI) demonstrated normal LV function with subepicardial late gadolinium enhancement (LGE) in the basal to mid inferolateral wall, concerning for acute myocarditis. Follow-up transthoracic echocardiography revealed normal LV size and function with normal strain, and repeat cardiac MRI showed complete resolution of LGE. She underwent maximal cardiopulmonary exercise testing (CPET), exercising for 13 minutes and 15 seconds, achieving 15 METs with a VO2 max of 40.4 mL/kg/min, which demonstrated frequent PVCs without nonsustained ventricular tachycardia (VT). Normal complete blood count and basic metabolic panel, aspartate aminotransferase, 38 U/L, alanine aminotransferase, 38 U/L, magnesium 2.2 mg/dL, thyroid-stimulating hormone, 1.96 μIU/mL, hemoglobin A1c, 5.8%.

Genotyping Method: Comprehensive genetic testing identified a pathogenic MYL2 variant.

FunctionalAnalysis: No functional analysis of the variant was performed

Variant: NM_000432.4:c.173G>A

ClinVar: 14067

CAID: CA009915

gnomAD: 12:111352091 C / T, chr12-110914287-C-T

AdditionalInfo: NR