Submissions for variant NM_000335.5(SCN5A):c.1672C>T (p.His558Tyr)

gnomAD frequency: 0.00001  dbSNP: rs966323009

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004004921	SCV004839346	uncertain significance	Cardiac arrhythmia	2023-11-02	criteria provided, single submitter	clinical testing	This missense variant replaces histidine with tyrosine at codon 558 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with epilepsy (PMID: 31696929). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV001254773	SCV001430875	uncertain significance	Sudden cardiac arrest	2020-04-07	no assertion criteria provided	research	This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband identified with this variant. For further information please feel free to contact us.