Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171052 | SCV000223616 | uncertain significance | not provided | 2013-09-10 | criteria provided, single submitter | clinical testing | p.Val158Met (GTG>ATG): c.472 G>A in exon 4 of the SCN1B gene (NM_001037.3). The Val158Met missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one uncharged, non-polar amino acid for another at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether Val158Met is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV002515234 | SCV003294912 | pathogenic | Brugada syndrome 5 | 2023-10-04 | criteria provided, single submitter | clinical testing | The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.4, and corresponds to NM_199037.3:c.*5042G>A in the primary transcript. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 158 of the SCN1B protein (p.Val158Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal recessive SCN1B-related conditions (PMID: 33901312). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects SCN1B function (PMID: 33901312). For these reasons, this variant has been classified as Pathogenic. |