Case - SCAS1: Korean, 66yo, Male

CasePresentingHPOs: HP:0012622 (chronic kidney disease,

CaseHPOFreeText: survived sudden cardiac arrest caused by idiopathic ventricular fibrillation, previous smoker, no evidence of cardiomyopathy in 2-D echocardiography, mild hypertrophic manifestation of cardiac septum

CaseNotHPOs: HP:0001677 (coronary artery disease)

CaseNotHPOFreeText: abnormal coronary angiography, positive spasm provocation test with ergonovine

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: Family history was recorded, daughter has congestive heart failure

CasePreviousTesting: electrocardiogram, two-dimensional echocardiography, coronary angiography or cardiac MRI, full testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing (supplementary data, table S3)

CaseGenotypingMethod: Genomic DNA extracted from peripheral blood leukocytes, WES, gene-specific analysis with an in silico gene panel composed of 100 genes including 96 channelopathy and cardiomyopathy genes, variants found in WES confirmed via PCR and Sanger Sequencing

Variant: NM_000257.3(MYH7):c.4130C>T (p.Thr1377Met)

ClinVar: 42992, https://www.ncbi.nlm.nih.gov/clinvar/variation/42992/

gnomAD: 0.000003977, https://gnomad.broadinstitute.org/variant/14-23887458-G-A

Supplementary Data table 1

Variant noted to be present in 4 individuals

Variant: NM_000257.3(MYH7):c.4130C>T (p.Thr1377Met)

ClinVar: 42992, https://www.ncbi.nlm.nih.gov/clinvar/variation/42992/

gnomAD: 0.000003977, https://gnomad.broadinstitute.org/variant/14-23887458-G-A

CaseIII-1: Male, China, Asian, 51 years report

CasePresentingHPOs: HP:0001962, HP:0100749, HP:0002094, HP:0500020, HP:0031185, HP:0004755, HP:0031295, HP:0011103 (Heart palpitations, Chest pain, Dyspnea, Abnormal cardiac biomarker test, Increased NT-proBNP level, Supraventricular tachycardia, Left atrial enlargement, Abnormality of the left ventricular outflow tract)

HPOsFreeText: Experienced palpitations for 9 years, Chest pain and mild dyspnea for 2 years, Slightly elevated cardiac troponin T level of 21.8 ng/L (normal 0 to 14 ng/L), Significantly elevated N-terminal pro-brain natriuretic peptide level of 537 pg./mL (normal 0 to 125 pg/mL), ECG showed non-specific ST_T change, Preserved biventricular systolic function, Severe LV outflow tract obstruction (peak aortic outflow velocity = 4.8 m/s, peak gradient = 92 mmHg), Proband had a sigmoid septum with LV outflow tract obstruction and LV mass index to body surface area (BSA) of 87.2 g/m2

CaseNotHPOs: HP:0001677 (Coronary artery disease)

NotHPOsFreeText: N/A

CaseAddInfo:

CaseGenotypingMethod: Genomic DNA was acquired from the proband and all surviving members of his extended family. These were all tested by a 117 gene screening panel that were connected to Cardiomyopathy. The results were confirmed by Sanger sequencing and the variants found were filtered for pathogenicity.

Variant: NM_000257.3:c.4130C>T (p.Thr1377Met)

ClinVar: 42992 https://www.ncbi.nlm.nih.gov/clinvar/variation/42992/

gnomAD: European (Non-Finnish) 8.791e-6, Overall 3.977e-6 https://gnomad.broadinstitute.org/variant/14-23887458-G-A

Segregation

Affected: 9

Unaffected: 17

Segregations: 23

PublishedLOD: N/A

eLOD: 6.92

AddSegInfo: 6 individuals died before this investigation so clinical data and phenotypes could not be collected, 10 individuals were genotype positive but phenotype negative

Case#: HCM490, female, 41 yrs, not a smoker

DiseaseAssertion: HCM

FamilyInfo: None

CasePresentingHPOs: 44mm LAD, 15mm LVST, 39mm LVEDD, 58% LVEF, 21mm Maxi LVWT, 63mmHg Maxi LVOTG, 109178274 raw RNA-seq reads, 102325212 HQ reads (93.72%), 96.79% mapping rate, 728218 total variant, 33873 exonic variant

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: RNA-seq, read mapping, variant calling, identify functional variants, differential expression analysis, miRWalk miRNA target prediction, LncRNA annotation, Co-expression network analysis, PPI network analysis, gene over-representation analysis,

Variant: NM_000257.4(MYH7):c.4130C>T (p.Thr1377Met)

ClinVar: 42992 https://www.ncbi.nlm.nih.gov/clinvar/variation/42992/

CAID: N/A

gnomAD: 0.000008791 European (non-finnish) https://gnomad.broadinstitute.org/variant/14-23887458-G-A