Hypothesis

The proband (II-9)

CaseII-9: Male, 38 years diagnosis, China, Asian

DiseaseAssertion: Hypertrophic cardiomyopathy

FamilyInfo: Proband's father (I-1) and mother (I-2) had histories of mild episodes of dizziness, no other symptoms reported in the other family members

CasePresentingHPOs: HP:0001279, HP:0001712, HP:0001639 (Syncope, Left ventricular hypertrophy, Hypertrophic cardiomyopathy)

HPOsFreeText: Heart rate 62 bpm, PR interval 172 ms, QRS complex duration 88 ms, Diffuse repolarization changes with a late-onset inverted T-wave pattern, LVMI 109.55 g/m2, MLVWT 24 mm, Ejection Fraction 70%

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: See Table 1

CaseGenotypingMethod: Genomic DNA was extracted from blood and amplified. It was then subjected to a sequencing panel with an Illumina sequencer based on the 96 genes related to cardiac function. All readings were aligned, with any variants confirmed by Sanger sequencing and filtered for pathogenicity.

Variant: NM_000257.3:c.5151T>A (p.His1717Gln)

CAID: CA389036862 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000257.3%3Ac.5151T%3EA

gnomAD: Not in gnomAD

Multiple Gene Variants:

KCNQ1 Variant

Variant: NM_000218.2:c.568C>T (p.Arg190Trp)

ClinVar: 53070 https://www.ncbi.nlm.nih.gov/clinvar/variation/53070/

gnomAD: Latino 2.896e-5, Overall 4.011e-6 https://gnomad.broadinstitute.org/variant/11-2591948-C-T

MYLK2 Variant

Variant: NM_033118.3:c.970A>G (p.Lys324Glu)

ClinVar: CA408526793 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_033118.3%3Ac.970A%3EG

gnomAD: African 6.453e-5, Overall 4.087e-6 https://gnomad.broadinstitute.org/variant/20-30412153-A-G