ClinVar Miner

Submissions for variant NM_001040151.2(SCN3B):c.199G>A (p.Glu67Lys)

gnomAD frequency: 0.00004  dbSNP: rs140381249
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497982 SCV000590162 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing Thee E67K variant has not been publishedas pathogenic or been reported as benign to our knowledge. This variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, sizeand/or other properties. In addition, this substitution occurs at a position that is conserved through mammals.Nonetheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to theprotein structure/function. Finally, this variant is observed in 6/66694 (0.009%) alleles from individuals of EuropeanNon-Finnish ancestry in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer).
Invitae RCV001372816 SCV001569505 uncertain significance Brugada syndrome 7 2020-06-07 criteria provided, single submitter clinical testing 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SCN3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 432438). This variant is present in population databases (rs140381249, ExAC 0.009%). This sequence change replaces glutamic acid with lysine at codon 67 of the SCN3B protein (p.Glu67Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.
Fulgent Genetics, Fulgent Genetics RCV001372816 SCV002777659 uncertain significance Brugada syndrome 7 2021-10-01 criteria provided, single submitter clinical testing
Dept of Medical Biology, Uskudar University RCV003318378 SCV004021953 uncertain significance Long QT syndrome 2024-01-08 criteria provided, single submitter research Criteria: PM2, BP4
Ambry Genetics RCV004023335 SCV005027574 uncertain significance Cardiovascular phenotype 2023-10-27 criteria provided, single submitter clinical testing The p.E67K variant (also known as c.199G>A), located in coding exon 2 of the SCN3B gene, results from a G to A substitution at nucleotide position 199. The glutamic acid at codon 67 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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