Submissions for variant NM_000334.4(SCN4A):c.2341G>A (p.Val781Ile)

gnomAD frequency: 0.00873  dbSNP: rs62070884

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078657	SCV000110513	benign	not specified	2013-07-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000078657	SCV000152633	benign	not specified	2016-05-04	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000078657	SCV000257669	benign	not specified	2015-06-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078657	SCV000303637	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000392057	SCV000405221	likely benign	Hypokalemic periodic paralysis, type 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000309597	SCV000405222	likely benign	Congenital myasthenic syndrome 16	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000368999	SCV000405223	likely benign	Potassium-aggravated myotonia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000020268	SCV000405224	likely benign	Hyperkalemic periodic paralysis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000315013	SCV000405225	likely benign	Paramyotonia congenita of Von Eulenburg	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000078657	SCV000520903	benign	not specified	2016-02-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514862	SCV000610280	likely benign	not provided	2017-07-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000020268	SCV000658532	benign	Hyperkalemic periodic paralysis	2025-02-03	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258245	SCV001435159	likely benign	Joubert syndrome 17		criteria provided, single submitter	research	The heterozygous p.Val781Ile variant in SCN4A has been identified in 2 individuals with hyperkalaemic periodic paralysis (PMID: 7695243, 18046642), and has been identified in >2% of Latino chromosomes and 9 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Val781Ile variant may not impact protein function (PMID: 9266738). However, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for hyperkalaemic periodic paralysis.
Fulgent Genetics, Fulgent Genetics	RCV002496423	SCV002802129	likely benign	Hypokalemic periodic paralysis, type 1; Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16	2022-04-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514862	SCV004138796	benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	SCN4A: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000514862	SCV005211234	likely benign	not provided		criteria provided, single submitter	not provided
GeneReviews	RCV000020268	SCV000040622	not provided	Hyperkalemic periodic paralysis		no assertion provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000078657	SCV001742129	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000514862	SCV001932524	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000514862	SCV002035576	likely benign	not provided		no assertion criteria provided	clinical testing