ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2341G>A (p.Val781Ile) (rs62070884)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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,PreventionGenetics RCV000078657 SCV000303637 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 Clinical Services Laboratory,Illumina RCV000309597 SCV000405222 likely benign Congenital myasthenic syndrome, acetazolamide-responsive 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 Clinical Services Laboratory,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 Clinical Services Laboratory,Illumina RCV000020268 SCV000405224 likely benign Familial 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 Clinical Services Laboratory,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.
Broad Institute Rare Disease Group, Broad Institute RCV000078657 SCV000574523 benign not specified 2016-11-20 criteria provided, single submitter reference population ACMG Criteria: BS1, BS2, ?BS3. Single case reported in literature (PMID: 7695243) in gene associated with autosomal dominant moderate/mild pediatric disease (hyperkalemic periodic paralysis). There is also negative functional data in a cell line (not necessarily a well established assay): "no alteration of channel activation, or any defect in either fast or slow inactivation" (PMID: 9266738). In ExAC, allele frequency is 2.9% in South Asians, and there are 9 homozygotes.
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
Invitae RCV000020268 SCV000658532 benign Familial hyperkalemic periodic paralysis 2020-12-07 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute 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.
GeneReviews RCV000020268 SCV000040622 benign Familial hyperkalemic periodic paralysis 2016-01-28 no assertion criteria 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

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