ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.73G>A (p.Asp25Asn)

gnomAD frequency: 0.00001  dbSNP: rs786205837
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171059 SCV000223623 pathogenic not provided 2012-02-17 criteria provided, single submitter clinical testing p.Asp25Asn (GAC>AAC): c.73 G>A in the SCN1B gene. The Asp25Asn missense mutation in the SCN1B gene was previously reported as a de novo mutation in a patient who presented with a partial epileptic crisis (Orrico et al., 2009), and the NHLBI ESP Exome Variant Project did not identify Asp25Asn in approximately 5000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Asp25Asn results in a non-conservative amino acid substitution, as a negatively charged Aspartic acid residue is replaced by an uncharged Asparagine residue. It alters a highly conserved position in the N-terminal region of the voltage-gated sodium channel protein Navß1, and a mutation at a neighboring codon (Leu28Ile) has been published in association with epilepsy (Klassen et al., 2011). The variant is found in EPILEPSY panel(s).
Ambry Genetics RCV001266526 SCV001444701 uncertain significance Inborn genetic diseases 2018-11-28 criteria provided, single submitter clinical testing
Invitae RCV002517646 SCV003443902 uncertain significance Brugada syndrome 5 2022-04-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 25 of the SCN1B protein (p.Asp25Asn). This variant is present in population databases (rs786205837, gnomAD 0.01%). This missense change has been observed in individual(s) with SCN1B-related conditions (PMID: 19522081). ClinVar contains an entry for this variant (Variation ID: 190879). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies have shown that this missense change affects SCN1B function (PMID: 29992740). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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