Supplementary Material 4

Case M-8: Japanese

DiseaseAssertion: idiopathic cardiomyopathy (HCM and DCM)

CasePreviousTesting: Clinical evaluation, chest radiography, electrocardiography, echocardiography, cardiac catheterization, full testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1)

CaseGenotypingMethod: 8 sarcomeric genes amplified from genomic DNA via PCR then screened using bidirectional direct sequencing

Variant: NM_000257.3(MYH7):c.1816G>A (p.Val606Met)

ClinVar: 14091, https://www.ncbi.nlm.nih.gov/clinvar/variation/14091/

gnomAD: 0.000007070, https://gnomad.broadinstitute.org/variant/14-23896866-C-T

Case#: HCM506, male, 19 yr, smoker

DiseaseAssertion: HCM

FamilyInfo: None

CasePresentingHPOs: 48mm LAD, 20mm LVST, 43mm LVEDD, 75% LVEF, 21mm Maxi LVWT, 59mmHg Maxi LVOTG, 104464396 raw RNA-seq reads, 98442104 HQ reads (94.24%), 96.88% mapping rate, 721500 total variant, 33453 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.1816G>A (p.Val606Met)

ClinVar: 14091 https://www.ncbi.nlm.nih.gov/clinvar/variation/14091/

CAID: N/A

gnomAD: 0.00001548 European (non-finnish) https://gnomad.broadinstitute.org/variant/14-23896866-C-T

Supplementary Data Table S3

Case: 145

DiseaseEntity: HCM

HPOsFreeText: left ventricular hypertrophy (LVH) ≥15 mm

InheritancePattern: n/a

CasePreviousTesting: MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1 (59 genes total tested)

CaseGenotypingMethod: NGS of 59 genes (Supplemental Table S1), pathogenic and likely pathogenic variants confirmed via Sanger Sequencing

Variant1: NM_000257.4(MYH7):c.1816G>A (p.Val606Met)

ClinVar: 14091 https://www.ncbi.nlm.nih.gov/clinvar/variation/14091/

gnomAD: 0.00001548, https://gnomad.broadinstitute.org/variant/14-23896866-C-T

Variant2: NM_000257.4(MYH7):c.3853+7C>T

ClinVar: 42977 https://www.ncbi.nlm.nih.gov/clinvar/variation/42977/

gnomAD: 0.003956, https://gnomad.broadinstitute.org/variant/14-23888685-G-A

MultipleGeneVariants:

(1) SDHA Variant

Variant: NM_004168.4(SDHA):c.1886A>T (p.Tyr629Phe)

ClinVar: 224949 https://www.ncbi.nlm.nih.gov/clinvar/variation/224949/

gnomAD: 0.5249, https://gnomad.broadinstitute.org/variant/5-254599-A-T

(2) TMPO Variant

Variant: NM_001032283.2(TMPO):c.859G>C (p.Ala287Pro)

ClinVar: 43693 https://www.ncbi.nlm.nih.gov/clinvar/variation/43693/

gnomAD: 0.04732, https://gnomad.broadinstitute.org/variant/12-98938295-G-C