Case III-4: Female, 4yo

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy)

CaseHPOFreeText: myocardium lesion, suspected double-chambered left ventricle, asymptomatic, normal thickness of septum and left ventricle, fibromuscular tissues left ventricular apex, left ventricle ventricle end-diastolic diameter = 38.4mm, left ventricular ejection fraction = 64%

CasePreviousTesting: same as proband

CaseGenotypingMethod: segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case III-1: Male, 11yo, proband, died at 12yo

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0002018, HP:0000969, HP:0003388, HP:0001640, HP:0002240, HP:0002240, HP:0005135, HP:0031295 (nausea, edema, fatigability, cardiomegaly, hepatomegaly, left ventricular hypertrophy, abnormal T-wave, left atrial enlargement)

CaseHPOFreeText: inability to lie down, double chambered left ventricle, protrusion of precordium, soft heart sounds, grade 3/6 systolic murmur at the cardiac apex, liver enlarged to 3cm below right costal margin, left ventricle divided into apical and basal chambers by an incomplete fibromuscular septum, basal chamber was enlarged (ball-shaped) and had end-diastolic diameter of 80.7mm, impaired contraction of of left ventricular wall and septum, reduction of left ventricular ejection fraction = 35%, diameter of communication between 2 chambers of left ventricle = 16.0mm, the apical chamber of the left ventricle had a thinning wall, relative dullness of cardiac enlargement, normal thickness of septum and left ventricular wall, upper and middle section of ventricular septum expanded to right ventricle, died due to multiple system organ failure

FamilyInfo: 8 family members with double-chambered left ventricles

CasePreviousTesting: transthoracic echocardiography, ECG, cardiac MRI

CaseGenotypingMethod: WES, Affymetrix Cytoscan 750K Array to check potential candidate copy number variations, segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case II-3: Female, 40yo

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy)

CaseHPOFreeText: double-chambered left ventricle, reduced exercise capacity for 13yrs, mild heart failure symptoms, normal thickness of septum and left ventricle, 2 chambers of left ventricle have 18.5mm diameter of communication and they contract almost normally, left ventricle ventricle end-diastolic diameter = 74.3mm, left ventricular ejection fraction = 45%

CasePreviousTesting: same as proband

CaseGenotypingMethod: segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case I-2: Female, 66yo, suspected to be the founder of the variant

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0001635 (heart failure)

CaseHPOFreeText: suspected double-chambered left ventricle

CasePreviousTesting: same as proband

CaseGenotypingMethod: segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case II-5: Female, 35yo

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0003388, HP:0001712 (fatigability, left ventricular hypertrophy)

CaseHPOFreeText: double-chambered left ventricle, normal thickness of septum and left ventricular wall, 2 chamber of left ventricle have 14.2mm diameter of communication and they both contract normally, left ventricle ventricle end-diastolic diameter = 59.9mm, left ventricular ejection fraction = 50%

CasePreviousTesting: same as proband

CaseGenotypingMethod: WES, segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case III-3: Female, 6yo

DiseaseAssertion: Left ventricular hypertrophy

CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy)

CaseHPOFreeText: double-chambered left ventricle, asymptomatic, normal thickness of septum and left ventricle, left ventricle ventricle end-diastolic diameter = 53.5mm, left ventricular ejection fraction = 64%

CasePreviousTesting: same as proband

CaseGenotypingMethod: Affymetrix Cytoscan 750K Array to check potential candidate copy number variations, segregation analysis using the results from Sanger sequencing

Variant: NM_000257.3:c.998A>T

CAID: CA389051586, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051586

gnomAD: n/a

Case: Male, 43yo

DiseaseAssertion: HCM

FamilyInfo: Variant (p.Val698Ala) segregates with HCM in 5 family members and 2 others are unaffected carriers

CaseHPOFreeText: left ventricular wall thickness = 28 mm

CasePreviousTesting: n/a

CaseGenotypingMethod: n/a

Variant: NM_000257.3(MYH7):c.2093T>C (p.Val698Ala) heterozygous

ClinVar: 42878, https://www.ncbi.nlm.nih.gov/clinvar/variation/42878/

gnomAD: n/a

Case: Pedigree 4 proband, congenital (abnormalities noticed at 24wks gestation), Yemenite Jewish

CasePresentingHPOs: HP:0012817, HP:0010316 (noncompaction cardiomyopathy, Ebstein anomaly)

HPOsFreeText: clinical severity: moderate to asymptomatic

CaseNotHPOs:

NotHPOsFreeText: skeletal involvement

CasePreviousTesting: none

CaseGenotypingMethod: MYH7 sequencing

Variant: NM_000257.4:c.1859T>C (p.Leu620Pro)

CAID: CA389049669, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389049669

gnomAD: n/a

FamilyInfo: father, the paternal grandmother, and paternal uncle had a known history of Ebstein anomaly and NCCM, proband's 2 sisters are healthy with no evidence of cardiomyopathy, 7 other family members diagnosed with Ebstein anomaly and NCCM, but most were asymptomatic, variant segregated with all affected members in heterozygous state, no unaffected members were genotype positive

Case 2.01: Family 2, Male, 35yo at follow-up

DiseaseAssertion: Hypertrophic cardiomyopathy

CaseHPOFreeText: maximum left ventricular wall thickness ≥ 13 mm, follow-up echo = 9mm, longitudinal stain follow-up = -17.5%

CaseNotHPOs: HP:0001712, HP:0011675, HP:0002094, HP:0100749 (left ventricular hypertrophy, arrhythmia, dyspnea, chest pain)

CasePreviousTesting: 2D and M mode echocardiographic measurements, electrocardiography, cardiac MRI, Holter monitoring, measurements of left ventricular wall thickness, cavity dimensions, structural abnormalities, systolic anterior movement of mitral leaflets, outflow gradients, and Doppler inflow parameters.

CaseGenotypingMethod: method not described

Variant: NM_000257.3(MYH7):c.1357C>T (p.Arg453Cys)

ClinVar: 14089, https://www.ncbi.nlm.nih.gov/clinvar/variation/14089/

gnomAD: n/a