Submissions for variant NM_001037.5(SCN1B):c.266G>A (p.Arg89His)

gnomAD frequency: 0.00001  dbSNP: rs138381632

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000171039	SCV000223603	uncertain significance	not provided	2023-07-24	criteria provided, single submitter	clinical testing	Observed as heterozygous variant in patient with primary electrical disease (Proost et al., 2017) and epilepsy (Dang et al., 2020); however, no further clinical information was provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28341588, 36291443, 32303391)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466397	SCV000545177	uncertain significance	Brugada syndrome 5	2024-01-25	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 89 of the SCN1B protein (p.Arg89His). This variant is present in population databases (rs138381632, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of autosomal dominant SCN1B-related conditions (PMID: 28341588; Invitae). ClinVar contains an entry for this variant (Variation ID: 190860). 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.
AiLife Diagnostics, AiLife Diagnostics	RCV000171039	SCV002501383	uncertain significance	not provided	2021-05-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002433738	SCV002744920	likely benign	Cardiovascular phenotype	2020-06-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV002485075	SCV002786283	uncertain significance	Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52	2021-11-08	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000171039	SCV004237152	uncertain significance	not provided	2023-02-07	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000171039	SCV001921737	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171039	SCV001954597	uncertain significance	not provided		no assertion criteria provided	clinical testing