ClinVar Miner

Submissions for variant NM_001040151.2(SCN3B):c.415C>T (p.Arg139Trp)

gnomAD frequency: 0.00003  dbSNP: rs368054375
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618849 SCV000737490 uncertain significance Cardiovascular phenotype 2021-12-08 criteria provided, single submitter clinical testing The p.R139W variant (also known as c.415C>T), located in coding exon 3 of the SCN3B gene, results from a C to T substitution at nucleotide position 415. The arginine at codon 139 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855267 SCV002196483 uncertain significance Brugada syndrome 7 2021-08-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 139 of the SCN3B protein (p.Arg139Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs368054375, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SCN3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 519233). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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