Case#: 17-year-old African American male

DiseaseAssertion: Symptomatic paroxysmal atrial fibrillation (AF)

FamilyInfo: Proband's mother experienced symptomatic early-onset paroxysmal AF at 47 years of age. Proband's maternal grandmother presented with minimally symptomatic AF at 52 years of age.

ParentalTesting: Proband, mother, and maternal grandmother tested positive for SCN5A variant.

CasePresentingHPOs: HP:0005110, HP:0004757

CaseHPOFreeText: Symptomatic paroxysmal atrial fibrillation. The initial presenting ECG revealed AF with controlled ventricular rates in the absence of atrioventricular (AV) nodal blockers.

CaseNotHPOs: HP:0001678

CaseNotHPOFreeText: absence of atrioventricular (AV) nodal blockers, LA and LV size normal.

CasePreviousTesting: NR

FunctionalAnalysis: The biophysical properties of the SCN5A-N470K mutant channel were investigated using voltage-clamp recordings following the transient transfection of HEK cells with either wild-type (WT) or N470K channels. The impact of the N470K mutation on the gating properties of the Nav1.5 sodium channel was also investigated. Findings indicate that a gain-of-function mutation.

Variant: 1410C>G (p.Asp470Lys)

ClinVar: 30047

CAID: CA014836

gnomAD: https://gnomad.broadinstitute.org/variant/3-38646328-G-C?dataset=gnomad_r2_1 (FAF: 0.0001656, African/African American)

AdditionalInfo: Clinical characteristics of proband and family members found in Table 1.