Case2: Male, 46 yrs onset, China, Asian

DiseaseAssertion: Arrhythmogenic Cardiomyopathy

FamilyInfo: Brother has ACM with dyskinesia and enlargement in RVOT and frequent VES, PKP2 variant segregated with disease but MYH7 variant was detected in 9 unaffected relatives (See Fig 3)

CasePresentingHPOs: HP:0001638, HP:0011675, HP:0010872, HP:0011712, HP:0004756, HP:0001962, HP:0002321, HP:0006682, HP:0001707 (Cardiomyopathy, Arrhythmia, T-wave inversion, Right bundle branch block, Ventricular tachycardia, Palpitations, Vertigo, Ventricular extrasystoles, Abnormality of the right ventricle)

HPOsFreeText: Task force score of 5, Regional right ventricular dyskinesia, PLAX RVOT is 43 mm, 1897 VES / 24 h, LVEF of 64%, LVEDD at 51 mm, IVS at 8 mm

CaseNotHPOs: HP:0001639, HP:0001711 (Hypertrophic cardiomyopathy, Abnormal morphology of the left ventricle)

NotHPOsFreeText: Depolarization abnormalities

CasePreviousTesting: Tested genes include MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC1, TTN, TCAP, ACTN2, LDB3, MYH6, TNNC1, MYPN and NEBL.

CaseGenotypingMethod: The coding sequences of 15 genes were directly captured and sequenced. Candidate variants were then filtered by pathogenicity and confirmed via sanger sequencing. Family members were tested via Sanger sequencing afterwards.

CaseAddInfo: Proband is heterozygous for both variants

Variant: NM_000257.3:c.5116C>G (p.Leu1706Val)

CAID: CA389036928 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389036928

gnomAD: Not in gnomAD

Multiple Gene Variants

(1) PKP2 Variant

Variant: NM_004572.3(PKP2):c.2489+1G>A

ClinVar: 6757 https://www.ncbi.nlm.nih.gov/clinvar/variation/6757/

gnomAD: 0.00008012, http://gnomad.broadinstitute.org/variant/12-32949042-C-T