Case#: Girl II.2 from family DCM84. Diagnosed in her third week of life. Ancestry NR.

DiseaseAssertion: Dilated cardiomyopathy with left ventricular noncompaction.

FamilyInfo: No known heart disease in her parents or older sister. None of them had the variant. See Figure 2.

ParentalTesting: Both parents tested negative by Sanger sequencing. They declined parentage testing. The authors think the variant likely arose de novo.

CasePresentingHPOs: HP:0001644, HP:0030682, HP:0025169, HP:0001635, HP:0001653, HP:0000980, HP:0001265, HP:0001252, HP:0000961, HP:0002094, HP:0001508

CaseHPOFreeText: She was pale and had trouble breathing. She also had cyanosis and low muscle tone. Her reflexes were reduced. Her first echo showed that both ventricles were enlarged. Her left ventricular ejection fraction was 20%. A later echo showed mitral regurgitation. She had trouble gaining weight. She died from heart failure at 3 years and 8 months.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

CasePreviousTesting: NR

Genotyping Method: Whole exome sequencing found the variant. Sanger sequencing was used to test her family.

FunctionalAnalysis: K30E made tropomyosin less stable. The thin filaments with K30E moved more slowly in the lab test. See Figures 3 through 5 and Tables 1 and 3.

Variant: NM_001018005.2(TPM1):c.88A>G (p.Lys30Glu). Heterozygous.

ClinVar: 3250489

CAID: NR

gnomAD: No record found in gnomAD v4.1.

AdditionalInfo: PMID 39684770. The variant was first called a VUS. After the lab tests the authors proposed that it was pathogenic. Supplementary Table S1 shows how her echo results changed over time.