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

TMEM70 Variant

Variant: NM_017866.5:c.440T>C (p.Ile147Thr)

ClinVar: 571761 https://www.ncbi.nlm.nih.gov/clinvar/variation/571761/

gnomAD: East Asian 4.893e-4, Overall 3.579e-5 https://gnomad.broadinstitute.org/variant/8-74893513-T-C

Case#: II-9, male, Asian, 38 yr, proband

DiseaseAssertion: HCM, LQT1

FamilyInfo: HCM passed on in family (figure 1)

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

CaseHPOFreeText: physical examination; 12-lead ECG (SR, HR 57 bpm, P 80 ms, PR 164 ms, QRS 102 ms, QTc 423 ms); 2D echocardiographic study with S5-1 probe (MLVWT 14 mm, EF 62%, LVMI 94.27 g/m^2);

CaseNotHPOs: HP:0030148 (Heart murmurs)

CaseNotHPOFreeText: No inverted T wave: Normal QTc 440 ms

CasePreviousTesting: Additional Sanger sequencing for KCNQ1, MKLY2, TMEM70

CaseGenotypingMethod: Illumina-SolexaHiSeq 2000 sequencing from peripheral blood leococytes; bi-directional Sanger sequencing;

Variant: absent

ClinVar: absent

CAID: CA389036862 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389036862

gnomAD: absent

MultipleGeneVariants:

(1) KCNQ1 Variant:

Variant: NM_181798.1(KCNQ1):c.187C>T (p.Arg63Trp)

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

CAID: n/a

gnomAD: absent

(2) MKLY2 Variant:

Variant: absent

ClinVar: absent

CAID: CA408526793 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA408526793

gnomAD: African 0.00006453 https://gnomad.broadinstitute.org/variant/20-30412153-A-G

(3) TMEM70 Variant:

Variant: NM_017866.6(TMEM70):c.440T>C (p.Ile147Thr)

ClinVar: 571761 https://www.ncbi.nlm.nih.gov/clinvar/variation/571761/

CAID: n/a

gnomAD: East Asian 0.0004893 https://gnomad.broadinstitute.org/variant/8-74893513-T-C