ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.13C>A (p.Leu5Met)

gnomAD frequency: 0.00001  dbSNP: rs1064796847
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478866 SCV000573974 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing The L5M variant in the SCN1B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected in presumably healthy individuals tested at GeneDx. The L5M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L5M as a variant of uncertain significance.
Invitae RCV001851271 SCV002258413 uncertain significance Brugada syndrome 5 2021-09-22 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 424188). This missense change has been observed in individual(s) with clinical features of SCN1B-related conditions (Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces leucine with methionine at codon 5 of the SCN1B protein (p.Leu5Met). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and methionine.
Ambry Genetics RCV002395181 SCV002700756 uncertain significance Cardiovascular phenotype 2020-06-08 criteria provided, single submitter clinical testing The p.L5M variant (also known as c.13C>A), located in coding exon 1 of the SCN1B gene, results from a C to A substitution at nucleotide position 13. The leucine at codon 5 is replaced by methionine, an amino acid with highly similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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