Case#: female, 43 yrs,

DiseaseAssertion: RCM

FamilyInfo: aunt had RCM, more symptom history in materal line

CasePresentingHPOs: Palpitations, atrial fibrillation, mitral regurgitation, left atrial enlargement, tricuspid regurgitation, pre-capillary pulmonary hypertension, abnormal thrombosis, ventricular extrasystoles, dyspnea, fatigue, pallor, circumoral cyanosis, jaundice, arrhythmia, hyponatremia, hypokalemia, hypoproteinemia, hyperbilirubinemia, decreased liver function (HP:0001962, HP:0005110, HP:0001653, HP:0031295, HP:0005180, HP:0033578, HP:0001977, HP:0006682, HP:0002094, HP:0012378, HP:0000980, HP:0032556, HP:0000952, HP:0011675, HP:0002902, HP:0002900, HP:0003075, HP:0002904, HP:0001410)

CaseHPOFreeText: QRS axis at 90 degrees; Q wave in DIII, negative T wave in DI, DII, DIII, aVF, V1-V6; left ventricular volume slightly reduced; mild mitral regurgitation; slight right ventricular longitudinal systolic dysfunction; mild tricuspid regurgitation; increased atrium volume; rare extrasystoles; juandice scleral; oxygen saturation level of 90%; spontaneous pain in hydrochondrium; enlarged liver; distended jugular veins; Na+=119 mmol/L; K+=3,4 mmol/L; serum total proteins=4,9 g/dL, serum albumin=2,6g/dL; direct bilirubin=0,53 mg/dL, indirect bilirubin=1,5 mg/dL, total bilirubin=2,08mg/dL; irregular liver contour and hyperechoic echostructure; dilated hepatic veins; 60,55% LVEF; 48,36ml/m^2 indexed EDV LV; 75,80ml/m^2 indexed EDV LA; 0,78 and 0,7m/s E wave; 133,131 ms deceleration time; 0,04 m/s LV septal S'; 0,07m/s RV wall S'; 20,13 mm TAPSE, 32, 43mmHg estimated sPAP;

CaseNotHPOs: N/A

CaseNotHPOFreeText: normal dimensions of aortic root, ascending root, diameter of left ventricle, right ventricular diameter, left ventricular wall thickness, right ventricular volume; normal LVEF; negative immunofixation and disease testing; moderate quantity of right pleural fluid;

CasePreviousTesting: N/A

CaseGenotypingMethod: ECG; oral anticoagulation, electric conversion to sinus rhythm; coronary angiography; immunofixation tests; storage disease testing; complete profile of biologic markers for autoimmune diseases; abdominal adipose tissue biopsy puncture; genetic testing; clinical examination; BP of 90/60mmHg and HR of 120 beats per minute;

Variant: MYH7(NM_000257.4):c.2162G>A (p.Arg721Lys)

ClinVar: absent

CAID: CA389049002 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389049002

gnomAD: absent

MultipleGeneVariants:

(1) ABCC9 Variant:

Variant: NM_005691.3(ABCC9):c.3557G>A (p.Arg1186Gln)

ClinVar: 201620 https://www.ncbi.nlm.nih.gov/clinvar/variation/201620/

CAID: N/A

gnomAD: 0.00008468 Latino/Admixed American https://gnomad.broadinstitute.org/variant/12-21991021-C-T

Supplementary Data Table S3

Case: 138

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

Variant: NM_000257.3:c.2162G>A (p.Arg721Lys)

CAID: CA389049002 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389049002

gnomAD: Not in gnomAD

MultipleGeneVariants:

(1) CRYAB Variant

Variant as listed does not exist on any transcript

Variant: c.331G>A (p.Gly111Ser)

ClinVar: N/A

gnomAD: N/A

(2) 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

(3) TCAP Variant

Variant: NM_003673.3(TCAP):c.458G>A (p.Arg153His)

ClinVar: 44710 https://www.ncbi.nlm.nih.gov/clinvar/variation/44710/

gnomAD: 0.002296, https://gnomad.broadinstitute.org/variant/17-37822316-G-A