CaseHCM083: 53 yrs report, Vietnam, Asian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: N/A

CasePresentingHPOs: HP:0002875, HP:0001712, HP:0001667, HP:0001705 (Exertional dyspnea, Left ventricular hypertrophy, Right ventricular hypertrophy, Right ventricular outlet obstruction)

HPOsFreeText: Maximal LV thickness 18 mm

CaseNotHPOs: HP:0005110, HP:0001297, HP:0004756 (Atrial fibrillation, Stroke, Ventricular tachycardia)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The gene panel included 10 sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC1, TNNC1, MYH6), 9 genes encoding Z-disk components and Ca2+ homeostasis factors (LDB3, CSRP3, TCAP, VCL, ACTN2, MYOZ2, NEXN, JPH2, PLN), and 4 genes involved in HCM phenocopies (GLA, LAMP2, PRKAG2, TTR), All probands had left ventricular wall thickness >= 15 mm and no other diseases that can cause secondary hypertrophy

CaseGenotypingMethod: The coding region, flanking sequences, and untranslated regions of each gene were enriched by LC-PCR, amplified, and sequenced on the Illumina MiSeq or MiniSeq platform. Identified variants were then filtered for pathogenicity and confirmed by Sanger sequencing.

Variant: NM_000257.4(MYH7):c.4159G>A (p.Glu1387Lys)

ClinVar: 181244 https://www.ncbi.nlm.nih.gov/clinvar/variation/181244/

gnomAD: 0.00003266, http://gnomad.broadinstitute.org/variant/14-23887429-C-T

Case#: II-9, female, 46 yrs

DiseaseAssertion: HCM

FamilyInfo: Yes, 2 siblings and niece have HCM

CasePresentingHPOs: chest tightness, palpitations (HP:0031352, HP:0001962)

CaseHPOFreeText: T flattened and inverted and left axis deviation (-48 degrees), 22mm MLVWT, 63% LVE F, 1.29 E/A ratio, LVOT-PG 4mm

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: sequencing, physical examination, ECG, 3D modeling, statistical analysis

MultipleGeneVariants:

(1) Variant: absent (MYH7- A934V)

ClinVar: N/A

CAID: CA389047003

gnomAD: absent

(2) Variant: NM_000257.4(MYH7):c.4159G>A (p.Glu1387Lys)

ClinVar: 181244 https://www.ncbi.nlm.nih.gov/clinvar/variation/181244/

CAID: N/A

gnomAD: 0.00003266 South Asian https://gnomad.broadinstitute.org/variant/14-23887429-C-T

CasePT-97: United States

CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

HPOsFreeText: N/A

CaseNotHPOs: HP:0001650, HP:0001658 (Aortic valve stenosis, Myocardial infarction)

NotHPOsFreeText: N/A

CaseAddInfo:

CaseGenotypingMethod: DNA was collected from the participants using blood samples. 18 genes suspected on contributing to HCM were targeted and sequenced. The variants were then located and filtered for pathogenicity.

Variant: NM_000257.3:c.4159G>A (p.Glu1387Lys)

ClinVar: 181244 https://www.ncbi.nlm.nih.gov/clinvar/variation/181244/

gnomAD: South Asian 3.266e-5, Overall 3.977e-6 https://gnomad.broadinstitute.org/variant/14-23887429-C-T