Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766769 | SCV000223628 | uncertain significance | not provided | 2022-11-04 | criteria provided, single submitter | clinical testing | Initially published as a pathogenic variant in an individual with atrial fibrillation, and functional studies show that D153N results in loss of function of the protein (Watanabe et al., 2009); however, as seizures were not reported in the affected individual, the association of D153N with epilepsy, if any, is unknown; Reported previously in two individuals in a large population cohort who had exome sequencing; the authors classified D153N as a variant of unknown significance (Dorschner et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Garde2020[CaseControl], 27435932, 24055113, 19808477, 21682648, 23838598, 34867379) |
Laboratory for Molecular Medicine, |
RCV000171064 | SCV000540269 | uncertain significance | not specified | 2016-10-20 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband with no segregations. In vitro functional study suggests variant results in loss of function; ClinVar: VUS by GeneDx |
Ambry Genetics | RCV000620098 | SCV000737774 | uncertain significance | Cardiovascular phenotype | 2021-11-12 | criteria provided, single submitter | clinical testing | The p.D153N variant (also known as c.457G>A), located in coding exon 4 of the SCN1B gene, results from a G to A substitution at nucleotide position 457. The aspartic acid at codon 153 is replaced by asparagine, an amino acid with highly similar properties. This variant has been described in an atrial fibrillation cohort with limited genes analyzed, and functional analyses suggested possible impact (Watanabe H et al. Circ Arrhythm Electrophysiol. 2009;2(3):268-75). In another study, this variant was detected in conjunction with other alterations in cardiovascular-related genes in a case of sudden unexplained death (Methner DN et al. Genome Res. 2016;26(9):1170-7). This variant was also reported as an incidental finding from 2 of 1000 participants' exomes and was classified as a variant of unknown significance (VUS) (Dorschner MO et al. Am J Hum Genet. 2013;93:631-40). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, the clinical significance of this variant for Brugada syndrome and autosomal recessive SCN1B-related early infantile epileptic encephalopathy is unclear; however, due to its observed frequencies in various cohorts, this variant is unlikely to be causative of autosomal dominant SCN1B-related epilepsy. |
Invitae | RCV001853079 | SCV002159046 | uncertain significance | Brugada syndrome 5 | 2023-12-22 | criteria provided, single submitter | clinical testing | The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.5, and corresponds to NM_199037.4:c.*5027G>A in the primary transcript. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 153 of the SCN1B protein (p.Asp153Asn). This variant is present in population databases (rs72550247, gnomAD 0.02%). This missense change has been observed in individual(s) with atrial fibrillation or sudden death (PMID: 19808477, 27435932). 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: 19808477). 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, |
RCV002477176 | SCV002792224 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52 | 2021-09-22 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000766769 | SCV003820754 | uncertain significance | not provided | 2020-10-13 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000054538 | SCV000083016 | pathogenic | Atrial fibrillation, familial, 13 | 2009-06-01 | no assertion criteria provided | literature only | |
Forensic Genetics Laboratory, |
RCV000234993 | SCV000263120 | pathogenic | Death in early adulthood | 2015-03-27 | no assertion criteria provided | clinical testing | NM_001037.4:c.457G>A is pathogenic for Death in early adulthood in combination with NM_198056.2:c.1844G>A |