Submissions for variant NM_000335.5(SCN5A):c.4218C>T (p.Ala1406=)

gnomAD frequency: 0.00001  dbSNP: rs373042738

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001718871	SCV000514552	uncertain significance	not provided	2025-02-25	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Color Diagnostics, LLC DBA Color Health	RCV001841297	SCV001348329	likely benign	Cardiac arrhythmia	2018-11-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001718871	SCV001661055	likely benign	not provided	2025-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002328923	SCV002630749	uncertain significance	Cardiovascular phenotype	2021-11-15	criteria provided, single submitter	clinical testing	The c.4221C>T variant (also known as p.A1407A), located in coding exon 22 of the SCN5A gene, results from a C to T substitution at nucleotide position 4221. This nucleotide substitution does not change the amino acid at codon 1407. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150202	SCV003838217	likely benign	Cardiomyopathy	2022-05-09	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001841297	SCV004823438	likely benign	Cardiac arrhythmia	2024-01-11	criteria provided, single submitter	clinical testing