CaseR858C: 44 year old (text states male, pedigree states female)

DiseaseAssertion: HCM

FamilyInfo: No family members manifested sudden death, lethal arrhythmia, LVOT obstruction, or severe heart failure.

One family member also carried double mutations

CaseHPOFreeText: greater LV hypertrophy than his family members who carried a single mutation

CasePreviousTesting: systematic mutation screening of eight sarcomeric genes: (MYH7), (MYBPC3), (TNNT2), (TNNI3), (MYL2), (MYL3), (TPM1), and (ACTC), using direct DNA sequencing

GenotypingMethod: Genomic DNA was isolated from the leukocytes of the peripheral blood. Polymerase chain reaction was used to amplify the exons and flanking intronic bases of the eight genes, including MYH7, MYBPC3, TNNT2, TNNI3, MYL2, and MYL3. When no mutation was found, analysis of the TPM1 and ACTC genes was performed

MultipleGeneVariants:

VariantMYH7: NM_000257.4:c.2572C>T

ClinVar: 164324

CAID: CA012656

gnomAD: https://gnomad.broadinstitute.org/variant/14-23894085-G-A

0.00006152 African

VariantTNNT2: NM_001001430.3:c.857G>A

ClinVar: 43677

CAID: CA005304

gnomAD: https://gnomad.broadinstitute.org/variant/1-201328348-C-T

0.0008699 East Asian

CaseBII-1: Male, 23 years diagnosis, China, Asian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: No family history, pedigree provided

CasePresentingHPOs: HP:0001639, HP:0100749 (Hypertrophic cardiomyopathy, Chest pain)

HPOsFreeText: Interventricular septal thickness at 15.6 mm, Left ventricular posterior wall thickness at 12.1 mm

CaseNotHPOs: N/A

NotHPOsFreeText: N/A

CaseAddInfo: Parents tested negative for variant, therefore it is asserted as de novo

CasePreviousTesting: See list of sequenced genes

CaseGenotypingMethod: Genomic DNA was isolated from whole blood of all patients and controls. Whole coding exons and exon-intron boundaries of the 19 HCM-related genes listed above were amplified and sequenced on Ion Torrent PGM. These variants were then filtered for pathogenicity and compared to the controls. Any mutations found were confirmed by conventional dideoxy sequencing and Sanger sequencing.

Variant: NM_000257.3:c.2572C>T (p.Arg858Cys)

ClinVar: 164324 https://www.ncbi.nlm.nih.gov/clinvar/variation/164324/

gnomAD: Not in gnomAD