Case#: N/A

DiseaseAssertion: inherited arrhythmia syndromes, including Brugada syndrome, progressive cardiac conduction disease, and congenital sick sinus syndrome.

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011704, HP:0011675

CaseHPOFreeText: H558R may be over-represented among patients with Brugada syndrome in the Chinese Han population, S524Y, has been described in individuals of African ancestry.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The antiarrhythmic drug mexiletine may have a therapeutic modulation of loss-of-function sodium channel defects; The antiarrhythmic drug mexiletine increased the expression level of both S524Y and H558R in Q1077 back to WT levels as demonstrated by current measurements and channel cell surface expression.

Genotyping Method: N/A

FunctionalAnalysis: N/A

Variant: SCN5A c.1571C>A (p.Ser524Tyr), SCN5A c.1673A>G (p.His558Arg)

ClinVar: 48286, 48289

CAID: CA014995, CA015145

gnomAD: p.Ser524Tyr - max AF: 0.03661 African American populations (https://gnomad.broadinstitute.org/variant/3-38604031-G-T?dataset=gnomad_r4), p.His558Arg - max AF: 0.3392 Amish populations (https://gnomad.broadinstitute.org/variant/3-38603929-T-C?dataset=gnomad_r4)