CaseHCM041: 50 yrs report, Vietnam, Asian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: N/A

CasePresentingHPOs: HP:0001712, HP:0100749, HP:0002875, HP:0011103, HP:0031295 (Left ventricular hypertrophy, Chest pain, Exertional dyspnea, Abnormality of the left ventricular outflow tract, Left atrial enlargement)

HPOsFreeText: Maximal LV thickness 30 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.1324C>T (p.Arg442Cys)

ClinVar: 177897 https://www.ncbi.nlm.nih.gov/clinvar/variation/177897/

gnomAD: 0.00005012, http://gnomad.broadinstitute.org/variant/14-23898247-G-A

Supplementary Data: S2 Table

Case 4: Spanish, 67yo, Female

DiseaseAssertion: Hypertrophic Cardiomyopathy

CasePreviousTesting: Full Testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data table S1

CaseGenotypingMethod: genomic DNA obtained from blood or saliva, PCR, Sanger Sequencing

Variant: NM_000257.3(MYH7):c.1324C>T (p.Arg442Cys)

ClinVar: 177897, https://www.ncbi.nlm.nih.gov/clinvar/variation/177897/

gnomAD: 0.00002121, https://gnomad.broadinstitute.org/variant/14-23898247-G-A

DiseaseAssertion: Hypertrophic Cardiomyopathy

VariantPreviousTesting: ACTC1, ACTN2, CSRP3, LAMP2, MYBPC3, MYH7, NEXN, PLN, TNNC1, TNNI3, TNNT2, TPM1, CAV3, GLA, MYL2, MYL3, MYOZ2, PRKAG2, and TTR were all tested via NGS.

VariantGenotypingMethod: Next-generation sequencing panels were used to sequence and read the genetic information of the 760 HCM probands for variants within exons and in +/- 10 nucleotides within the flanking introns of the genes provided above. These variants were then interpreted and filtered for pathogenicity.

VariantAddInfo: Seen in one proband

Variant: NM_000257.4(MYH7):c.1324C>T (p.Arg442Cys)

ClinVarID: 177897 https://www.ncbi.nlm.nih.gov/clinvar/variation/177897/

gnomAD: 0.00005012, http://gnomad.broadinstitute.org/variant/14-23898247-G-A