ClinVar Miner

Submissions for variant NM_004588.5(SCN2B):c.578C>G (p.Thr193Arg) (rs115353159)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458076 SCV000548694 uncertain significance Atrial fibrillation, familial, 14 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 193 of the SCN2B protein (p.Thr193Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs115353159, ExAC 0.01%) but has not been reported in the literature in individuals with a SCN2B-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000490011 SCV000576994 uncertain significance not provided 2017-04-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN2B gene. The T193R variant has not been published as pathogenic or been reported as benign to our knowledge. This variant has been observed in 1/10,406 (0.01%) alleles from individuals of African ancestry, and in 4/66,736 (0.006%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T193R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

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