Functional implications of a rare variant in the sodium channel β1B subunit (SCN1B) in a 5-month-old male sudden infant death syndrome case

Key Teaching Points • Sudden infant death syndrome (SIDS) is defined as the sudden death of a healthy infant younger than 1 year of age without any obvious cause of death. Despite intensive genetic investigations, the underlying pathophysiological mechanism still remains elusive in most of the cases. • Whole-exome sequencing in a 5-month-old male infant identified a heterozygous missense variant in the β1B subunit of SCN1B. Electrophysiological recordings of Nav1.5 co-expressed with the β1B subunit variant p.R225C induced a loss of function of Nav1.5 channels. • The loss of function might have contributed to the sudden death event in this infant; however, further investigations are needed. This study demonstrates the importance of careful evaluation of likely pathogenic variants identified within next-generation sequencing approaches for an accurate interpretation of genetic results.