Submissions for variant NM_000334.4(SCN4A):c.2748C>G (p.Asn916Lys)

gnomAD frequency: 0.00253  dbSNP: rs115379510

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174672	SCV000226013	likely benign	not specified	2014-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000710210	SCV000530033	likely benign	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710210	SCV000615074	benign	not provided	2017-09-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085657	SCV000658542	benign	Hyperkalemic periodic paralysis	2025-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516640	SCV003660532	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.2748C>G (p.N916K) alteration is located in exon 14 (coding exon 14) of the SCN4A gene. This alteration results from a C to G substitution at nucleotide position 2748, causing the asparagine (N) at amino acid position 916 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174672	SCV005726197	likely benign	not specified	2024-11-19	criteria provided, single submitter	clinical testing	Variant summary: SCN4A c.2748C>G (p.Asn916Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00061 in 249238 control chromosomes, predominantly at a frequency of 0.0091 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 8.14 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN4A causing Congenital Myopathy 22A, Classic phenotype (0.0011). To our knowledge, no occurrence of c.2748C>G in individuals affected with Congenital Myopathy 22A, Classic and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 194329). Based on the evidence outlined above, the variant was classified as likely benign.