Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171047 | SCV000223611 | uncertain significance | not provided | 2016-12-06 | criteria provided, single submitter | clinical testing | p.Val8Leu (GTG>CTG): c.22 G>C in exon 1 of the SCN1B gene (NM_001037.3). The Val8Leu variant in the SCN1B gene has not been published as a disease-causing mutation or as a benign polymorphism to our knowledge. Val8Leu results in a conservative amino acid substitution of one non-polar amino acid for another at a position that is not well conserved across species, however there were few regions of homology in inter-species alignment. In silico analysis predicts that Val8Leu is benign. In addition, there are no nearby mutations in this region of the SCN1B gene. However, the NHLBI ESP Exome Variant Server reports Val8Leu was not observed in approximately 1000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Val8Leu is a disease-causing mutation or a rare benign variant. Brugada syndrome is most frequently caused by mutations in the genes encoding cardiac ion channel proteins, which regulate sodium and calcium movement in and out of cardiac cells (Fowler S et al., 2008; Hedley P et al., 2009). Although rare, mutations SCN1B have been reported previously in association with Brugada syndrome (Watanabe H et al., 2008). The variant is found in BRUGADA panel(s). |
Invitae | RCV003765068 | SCV004615639 | uncertain significance | Brugada syndrome 5 | 2023-09-10 | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 190867). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 8 of the SCN1B protein (p.Val8Leu). |