CaseA: Female, 49 yrs report

DiseaseEntity: Hypertrophic Cardiomyopathy (AD)

FamilyInfo: Has a monozygotic twin sister w/ same genotype and similar phenotype who lived far apart and had different living environments / life habits, Other family members were diagnosed with HCM afterwards and were genotype positive, See Figure 3 for pedigree

CasePresentingHPOs: HP:0001962, HP:0002875, HP:0001639, HP:0005110, HP:0031185, HP:0011713, HP:0001670, HP:0031295, HP:0030718, HP:0006683, HP:0001712 (Palpitations, Exertional dyspnea, Hypertrophic cardiomyopathy, Atrial fibrillation, Increased NT-proBNP level, Left bundle branch block, Asymmetric septal hypertrophy, Left atrial enlargement, Right atrial enlargement, Abnormal ventricular filling, Left ventricular hypertrophy)

HPOsFreeText: N/A

CaseNotHPOs: HP:0031480 (Abnormal mitral valve leaflet morphology)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: Elevated cardiac troponin T (cTnT) (19 ng/L; reference 0-14), Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) (10,214 pg/mL; reference 0-88 pg/mL), Electrocardiogram (ECG) and multi-modality imaging

CaseGenotypingMethod: Whole exome sequencing was performed in the twins using Illumina Hiseq 2500. Low quality variations were filtered and analysed to find potentially pathogenic mutations. The findings were then confirmed using Sanger sequencing.

Variant: NM_000257.4(MYH7):c.2302G>A (p.Gly768Arg)

ClinVar: 164337 https://www.ncbi.nlm.nih.gov/clinvar/variation/164337/

gnomAD: Not in gnomAD

Table V

Case 905: Italian, Male, 30yo at onset

DiseaseAssertion: HCM

FamilyInfo: family history of HCM

CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy)

CaseHPOFreeText: maximum left ventricular wall thickness of ≥15 mm, automatic implantable cardioverter defibrillator, heart transplantation

CasePreviousTesting: echocardiography, Full testing (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC1), additional testing: (GLA, LAMP2, PRKAG2), additional genes added with NGS: (TNNC1, MYH6, MYOM1, MYOZ2, ANKRD1, VCL, CALR3, CAV3)

CaseGenotypingMethod: Genomic DNA extracted from peripheral leukocytes, Sanger sequencing (73 samples), Next-gen sequencing (19 samples)

Variant: NM_000257.3(MYH7):c.2302G>A (p.Gly768Arg)

ClinVar: 164337, https://www.ncbi.nlm.nih.gov/clinvar/variation/164337/

gnomAD: n/a

MultipleGeneVariants:

(1) MYOM1 Variant:

Variant: NM_003803.3:c.1655G>A

CAID: CA401714383, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401714383

gnomAD: n/a