ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.134G>A (p.Arg45His)

gnomAD frequency: 0.00003  dbSNP: rs180943300
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171036 SCV000223600 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1B gene. The R45H variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 3/34418 (0.02%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016). The R45H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support adeleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000559019 SCV000647850 uncertain significance Brugada syndrome 5 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 45 of the SCN1B protein (p.Arg45His). This variant is present in population databases (rs180943300, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 190857). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV000765438 SCV000896727 uncertain significance Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002381546 SCV002693353 uncertain significance Cardiovascular phenotype 2023-06-14 criteria provided, single submitter clinical testing The p.R45H variant (also known as c.134G>A), located in coding exon 2 of the SCN1B gene, results from a G to A substitution at nucleotide position 134. The arginine at codon 45 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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