Case#: Single case; 37-year-old male construction worker; sudden unexplained death (SUD); found dead in bed ~1 hr after lunch, August 2005; molecular autopsy via WES in 2019 from autopsy tissue

DiseaseAssertion: Sudden unexplained death (SUD); no structural cardiac cause at autopsy; MYBPC3/TTN/ACADVL/RYR2-related per WES reevaluation

FamilyInfo: No family history or segregation data reported. The paper is a single molecular autopsy; no relatives were genotyped or phenotyped. No pedigree assessment performed.

ParentalTesting: Not performed, no family members tested.

CasePresentingHPOs: HP:0001698 (Sudden cardiac death); HP:0004756 (Ventricular tachycardia), the latter only as a speculative arrhythmic mechanism, not a documented clinical event

CaseHPOFreeText: Found dead in bed ~1 hr after lunch in August 2005. External examination showed no traumatic injury; toxicological blood screen negative. Clinical history unremarkable. Heart weighed 350 g (reference 331±57 g in men) with regular morphology and volume. Microscopy showed small foci of interstitial fibrosis, deemed not significant. No other organ showed significant abnormality. Case dismissed as SUD, reevaluated in 2019.

CaseNotHPOs: HP:0001639; HP:0001644; HP:0004308; HP:0001279

CaseNotHPOFreeText: No structural cardiac disease at autopsy, no hypertrophy, no dilation, normal heart morphology and volume. No evidence of any cardiomyopathy phenotype. No documented arrhythmia or syncope in life.

CasePreviousTesting: Autopsy (2005) with toxicology, histology. WES (2019) on DNA from FFPE left ventricular tissue; 562-gene cardiac panel (234 SCD/heart-disease genes + 328 heart-expressed genes); filtering against gnomAD (rare = MAF <0.1%); in silico prediction with DANN, MutationTaster, FATHMM, MutationAssessor, PolyPhen-2, SIFT, PROVEAN; ACMG 2015 classification; WebGestalt enrichment analysis.

Genotyping Method: WES on Illumina 500 (TruSeq library prep, xGen exome capture), SeqMule pipeline, ENLIS Genome Research annotation; variants confirmed by Sanger sequencing. Aligned to GRCh37.

FunctionalAnalysis: None performed by the authors, no functional assays in this paper. (ACADVL p.V383A residual activity ~20% is cited from a 2007 external study, not performed here.)

Variant: Four heterozygous missense variants, one per gene

ClinVar:926037

CAID: CA221696968

gnomAD: N/A

AdditionalInfo:N/A