Case1: 2-year-old female

DiseaseAssertion: restrictive cardiomyopathy, dilated cardiomyopathy

FamilyInfo:The maternal family history was negative for any form of cardiomyopathy or sudden death. Paternal family history was unknown, the mother (1-II:2) and maternal half-brother (1-III:2) were both heterozygous for the TNNI3 p.Arg136∗ variant, mother (1-II:2, age 20) and half-brother (1-III:2, age 21 months) demonstrated normal heart function on echocardiography. ParentalTesting: Clinical exome sequencing done on mother of proband

CasePresentingHPOs: HP:0032025, HP:0002140, HP:0005180, HP:0001653, HP:0005117

CaseHPOFreeText: left-sided facial and extremity weakness, enlarged cardiac silhouette with interstitial opacities, dilated left and right atria, unusual morphology of the chordae tendineae of both atrioventricular valves was noted, leading to a tethering phenomenon

CaseNotHPOs: HP:0001712,

CaseNotHPOFreeText: normal systolic function

CasePreviousTesting: Chest Xray, Echocardiogram, Head CT

Genotyping Method: clinical exome sequencing

FunctionalAnalysis: Immunostaining on heart tissue from patient, Quantitative analysis of heart tissue, Transmission electron microscopy with immersion fixed heart samples

Variant:homozygous TNNI3 nonsense variant, c.406C>T (p.Arg136∗)

ClinVar:488853

CAID:CA407440677

gnomAD:chr19-55154173-G-A v4

Case1: 6 year old, female

DiseaseAssertion: Restrictive cardiomyopathy

FamilyInfo:Both parents were heterozygous carriers, supporting an autosomal recessive inheritance pattern, younger brother showed no abnormalities or signs of the same illness

ParentalTesting: Sanger Sequencing

CasePresentingHPOs:HP:0002094, HP:0012378

CaseHPOFreeText: well below normal weight and height range for patients age, preserved systolic function and diastolic dysfunction, revealed preserved left ventricular systolic function with an ejection fraction, impaired diastolic function, enlarged atrium, wall thickening, impaired ventricular filling

CaseNotHPOs: NR

CaseNotHPOFreeText: comprehensive initial workup, including blood tests and urinalysis, revealed no additional abnormalities

CasePreviousTesting: Echocardiogram, blood tests, urinalysis

Genotyping Method: Whole-exome sequencing

FunctionalAnalysis: NR

Variant: TNNI3 c.406 C > T:p.R136

ClinVar: 488853

gnomAD: not found