No. of patient (gender)Age at onset (years)LVWT (mm)AICD (yes, no)Family history of HCM/SCD (yes, no/yes, no)Other medical (recurrent or episodic) issuesLVEF (%)Mutations#890 (F)72<15aNoNo/noAortic root enlargement History of hypertension; Intermittent LBBB~50LAMP2: c.661G>A p.(Gly221Arg)#892 (F)3019NoNo/noLGE at CMR imaging; hypercholesterolemia; NSVT61MYBPC3: c.1505G>A p.(Arg502Gln) MYBPC3: c.1564G>A p.(Ala522Thr) MYBPC3: c.2311G>A p.(Val771Met)#894 (M)624NoNo/noT2DM60MYBPC3: c.2429G>A p.(Arg810His)#895 (M)58<15bYesYes/noNone26MYBPC3: c.2309-2A>G#898 (F)111NoYes/noNone70MYH7: c.5302G>A p.(Glu1768Lys)#902 (F)2519YesNo/noHypothyroidism PVC, NSVT64MYH7: c.2507T>C p.(Ile836Thr)#903 (F)5218YesNo/noMyasthenia gravis, T2DM, HepC, PVC, PACs, PSVT, SND59MYOZ2: c.488T>C p.(Leu163Ser)#905 (M)30NAYesYes/noH-txNAMYH7: c.2302G>C p.(Gly768Arg) MYOM1: c.1655G>A p.(Gly552Asp)#906 (F)5815NoNo/noNoneNAMYBPC3: c.3617G>A p.(Gly1206Asp)#907 (M)37<15aNoNo/noECG abnormalities60MYOM1: c.432-1G>T#908 (M)20<15bNoYes/noH-tx, T2DM50MYH6: c.5111C>T p.(Ala1704Val)#909 (M)31<15aNoYes/noNone75MYBPC3: c.1409G>A p.(Arg470Gln)#910 (F)1723NoNo/noNone76MYBPC3: c.639C>A p.(Tyr213*)#913 (M)1219NoNo/noAngiokeratomas right ear hearing loss Visual impairment hypothyroidism, AF, NSVT60MYBPC3: c.649A>G p.(Ser217Gly) GLA: c.718_719delAA p.(Lys240Glufs*9) MYH6: c.3883G>C p.(Glu1295Gln)914 (M)2234YesNo/noHOCM, LGE at CMR imaging, NSVT65MYBPC3: c.506-2A>C { label (or @symbol) needed for fn[@id='tfn12-ijmm-38-04-1111'] } Bold font indicates mutations in MYH6 and in genes encoding non-TTm proteins that would not been identified without NGS analysis. a Diagnosis of borderline HCM; b original diagnosis of borderline HCM has been modified in dilated cardiomyopathy. PAC, premature atrial contractions; H-tx, heart transplantation; T2DM, type 2 diabetes mellitus; LVWT, left ventricular wall thickness; SND, sinus node dysfunction; AF, atrial fibrillation; hep C, hepatitis C; LBBB, left bundle branch block; AICD, automatic implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; SCD, sudden cardiac death; LGE, late gadolinium enhancement; CMR, cardiac magnetic risonance; NSVT, non-sustained ventricular tachycardia; PVC, premature ventricular contractions; HOCM, hypertrophic obstructive cardiomyopathy; PSVT, paroxysmal supraventricular tachycardia; NA, not available; NGS, next generation sequencing; HCM, hypertrophic cardiomyopathy.
Case: Cecconi_Patient#905, male, 30 yrs old at onset of HCM
CasePresentingHPOs:
CasePresentingHPOsFreeText: In adults, a maximal LV wall thickness (LVWT) ≥15 mm (not provided for this proband); the maximal LVWT between 10 and 14 mm, in conjunction with other features (i.e., family history, electrocardiogram abnormalities) prompted the diagnosis of borderline HCM. LVEF is not provided. Family history of HCM.
CaseNOTHPOs:
CaseNOTHPOSFreeText: no family history of SCD
CasePreviousTesting: The clinical diagnosis of primary HCM was based on medical history, a physical examination and on the echocardiographic demonstration of a hypertrophied left ventricle (LV) that could not be explained by another cardiac or systemic disease.
CaseGenotypingMethod: NGS, Sanger Targeted NGS panel to simultaneously analyze a total of 19 genes encoding not only TTm proteins, but also other sarcomeric proteins and some non-sarcomeric proteins that cause HCM phenocopies. Sanger sequencing to ensure a depth of coverage >20X for each target nucleotide.
Variant: c.1655G>A p.(Gly552Asp)
ClinVarID: or CAID: CA401714383
gnomAD: This proband has a missense variant, Gly552Asp. Not present in gnomAD. Proband has a variant in another HCM gene-MYH7.
AddCaseInfo: history of heart transplant, automatic implantable cardioverter defibrillator
PreviouslyPublished: no
VariantEvidence: none