CaseBII-3: Female, 64 years diagnosis, Italy, Caucasian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: See Figure 1

CasePresentingHPOs: HP:0001639, HP:0002094 (Hypertrophic cardiomyopathy, Dyspnea)

HPOsFreeText: Max Left ventricular wall thickness of 19 mm, Left atrium diameter of 42 mm, Left ventricular ejection fraction of 64%

CaseNotHPOs: HP:0003115, HP:0011675 (Abnormal ECG, Arrhythmia)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The ACM proband from Family B was genotyped for PKP2, DSP, DSC2, DSG2, JUP and CTNNA3; the HCM patient from Family B was genotyped for MYBPC3, MYH7, TNNI3 and TNNT2.

CaseGenotypingMethod: All patients in Family B were directly sequenced according to the found variants in CTNNA3 and MYH7. These variants were filtered for pathogenicity and prevalence and classified accordingly.

Variant: NM_000257.3:c.2631G>T (p.Met877Ile)

ClinVar: 417718 https://www.ncbi.nlm.nih.gov/clinvar/variation/417718/

gnomAD: Not in gnomAD

CaseBII-1: Female, 64 years diagnosis, Italy, Caucasian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: See Figure 1

CasePresentingHPOs: HP:0005110, HP:0001639, HP:0004756, HP:0001712, HP:0005135, HP:0002094, HP:0001962, HP:0006682, HP:0001279, HP:0000821 (Atrial fibrillation, Hypertrophic cardiomyopathy, Ventricular tachycardia, Left ventricular hypertrophy, Abnormal T-wave, Dyspnea, Palpitations, Premature ventricular contractions, Syncope, Hypothyroidism)

HPOsFreeText: Widespread septal and apical late gadolinium enhancement, Max Left ventricular wall thickness of 20 mm, Left atrium diameter of 54 mm, Left ventricular ejection fraction of 56%, Apical aneurism, Latent tuberculosis

CaseNotHPOs: N/A

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The ACM proband from Family B was genotyped for PKP2, DSP, DSC2, DSG2, JUP and CTNNA3; the HCM patient from Family B was genotyped for MYBPC3, MYH7, TNNI3 and TNNT2.

CaseGenotypingMethod: All patients in Family B were directly sequenced according to the found variants in CTNNA3 and MYH7. These variants were filtered for pathogenicity and prevalence and classified accordingly.

Variant: NM_000257.3:c.2631G>T (p.Met877Ile)

ClinVar: 417718 https://www.ncbi.nlm.nih.gov/clinvar/variation/417718/

gnomAD: Not in gnomAD

CaseBII-7: Male, 50 years diagnosis, Italy, Caucasian

DiseaseAssertion: Borderline Arrhythmogenic Cardiomyopathy

FamilyInfo: See Figure 1

CasePresentingHPOs: HP:0005133, HP:0006683 (Right ventricular dilatation, Abnormal ventricular filling)

HPOsFreeText: LVWT of 12 mm with an abnormal filling pattern, Mild right ventricular dilatation of 30  mm, Left atrium diameter at 45 mm, 62% ejection fraction

CaseNotHPOs: HP:0003115 (Abnormal ECG)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The ACM proband from Family B was genotyped for PKP2, DSP, DSC2, DSG2, JUP and CTNNA3; the HCM patient from Family B was genotyped for MYBPC3, MYH7, TNNI3 and TNNT2.

CaseGenotypingMethod: All patients in Family B were directly sequenced according to the found variants in CTNNA3 and MYH7. These variants were filtered for pathogenicity and prevalence and classified accordingly.

Variant: NM_000257.3:c.2631G>T (p.Met877Ile)

ClinVar: 417718 https://www.ncbi.nlm.nih.gov/clinvar/variation/417718/

gnomAD: Not in gnomAD

Multiple Gene Variants

CTNNA3 Variant:

Variant: NM_013266.3:c.2296_2298delTTG (p.Leu766del)

ClinVar: 100657 https://www.ncbi.nlm.nih.gov/clinvar/variation/100657/

gnomAD: Not in gnomAD