Case3: 73 year old man

DiseaseAssertion: He carried the MYL2 p.Ala13Thr variant

FamilyInfo: Yes, his wife, son, and daughter

ParentalTesting: Yes with screening by ECG and Echocardiography; underwent 12-lead electrocardiography (ECG), echocardiography (M-mode, 2D, and Doppler), and cardiac magnetic resonance imaging (CMR).

CasePresentingHPOs: HP:0002094, HP:0003388, HP:0012828, HP:0001650, HP:0034313, HP:0030882

CaseHPOFreeText: presented with dyspnea on exertion and easy fatigability. He was found to have severe aortic stenosis with an aortic valve area of 1 cm2 and a peak gradient of 68 mmHg. He had mild LVH with a wall thickness of 13 mm on an echocardiogram and a left ventricular ejection fraction (LVEF) of > 70%. A 12-lead ECG was unremarkable without evidence of LVH. He also had an 80% luminal diameter stenosis of left anterior descending coronary artery on coronary angiography. He underwent aortic valve replacement and a single vessel coronary artery bypass surgery. He has been asymptomatic since surgery

CaseNotHPOs:NR

CaseNotHPOFreeText:NR

CasePreviousTesting: Whole exome sequencing (WES)

Genotyping Method: Sanger sequencing

FunctionalAnalysis:NR

Variant:NM_000432.4:c.37G>A

ClinVar:14064

CAID:CA010242

gnomAD: gnomAD v2 12:111356964 C / T , gnomAD v3 12:110919160 C / T ,gmonAD v4 chr12-110919160-C-T

AdditionalInfo:NR

Case4: 43 year old woman.

DiseaseAssertion: diagnosed with HCM and carried variants in TTN, ALPK3, and MYL2 (p.Ala13Thr).

FamilyInfo:Other family members, II-1 is a 72-year old woman with history of intermittent atrial flutter with a normal interventricular septal thickness (8 mm) and a normal LVEF (58%). Likewise, individual II-4 is an asymptomatic 70-year old male, who had normal ECG, echocardiogram, and myocardial stress perfusion tomography. Proband’s children (IV-1 and IV-2) were asymptomatic and had normal ECGs and echocardiograms on the last evaluation. Likewise, individual IV-3 was a 7-year old asymptomatic boy who had a normal ECG and echocardiogram.

ParentalTesting: Yes, mother, brother, and father were tested

CasePresentingHPOs:HP:0031664, HP:0012835, HP:0004972, HP:0001670, HP:0034313, HP:0031656, HP:0012825

CaseHPOFreeText: Her physical exam was notable for the presence of a II/VI mid-systolic ejection murmur at left sternal border that radiated toward base of the heart. She also had a mildly elevated arterial blood pressure. A 12-lead ECG showed evidence of LVH, interventricular conduction delay, and repolarization abnormalities. An echocardiogram showed severe asymmetric septal hypertrophy with a hyperdynamic LV systolic function, systolic anterior motion of the mitral leaflet, and a LVOT gradient of 60 to 70 mmHg at rest (Figure 3B). CMR findings were also notable for asymmetric septal hypertrophy and mild patchy hyperenhancement.

CaseNotHPOs:NR

CaseNotHPOFreeText:NR

CasePreviousTesting: Whole exome sequencing (WES)

Genotyping Method: Sanger sequencing

FunctionalAnalysis:NR

Variant:NM_000432.4:c.37G>A

ClinVar:14064

CAID:CA010242

gnomAD: gnomAD v2 12:111356964 C / T , gnomAD v3 12:110919160 C / T ,gmonAD v4 chr12-110919160-C-T

AdditionalInfo:NR