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SCN5A has been implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) through isolated case observations. A single heterozygous SCN5A variant, c.677C>T (p.Ala226Val), was identified in one pediatric CPVT patient in a Chinese cohort of 95 children (PMID:38053087). No further unrelated CPVT probands carrying SCN5A‐only variants or familial segregation data have been reported, and no recurrent or founder SCN5A alleles specific to CPVT have been described.
Mechanistic studies of SCN5A predominantly address its role in long QT syndrome and Brugada syndrome, with no CPVT‐specific functional assays. A recent ClinGen Channelopathy Expert Panel reappraisal designated SCN5A as a disputed CPVT gene due to lack of phenotype‐representative evidence and absence of concordant functional data (PMID:34557911).
Key Take‐home: Current evidence does not support inclusion of SCN5A in isolated CPVT testing panels given the minimal case data and expert consensus disputing its causative role.
Gene–Disease AssociationDisputedSCN5A variants reported in <10 unrelated CPVT probands with no segregation or de novo evidence; Expert Panel classification as disputed ([PMID:34557911]) Genetic EvidenceLimitedA single SCN5A variant (c.677C>T (p.Ala226Val)) identified in one CPVT case with no familial segregation or additional probands ([PMID:38053087]) Functional EvidenceLimitedFunctional assays of SCN5A exist for LQT3 and Brugada syndrome but no CPVT‐specific channel studies |