Submissions for variant NM_001037.5(SCN1B):c.265C>T (p.Arg89Cys)

gnomAD frequency: 0.00004  dbSNP: rs766910280

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Medicine Lab, University of California San Francisco	RCV001007883	SCV001167587	uncertain significance	Generalized epilepsy with febrile seizures plus, type 1	2018-08-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001050500	SCV001214610	pathogenic	Brugada syndrome 5	2024-09-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 89 of the SCN1B protein (p.Arg89Cys). This variant is present in population databases (rs766910280, gnomAD 0.005%). This missense change has been observed in individuals with clinical features of autosomal recessive developmental and epileptic encephalopathy (PMID: 31465153; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 816882). 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. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001766822	SCV001991643	uncertain significance	not provided	2024-09-10	criteria provided, single submitter	clinical testing	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: Chunling2023[Article], 33084218, 31465153, 36684540)
Ambry Genetics	RCV002454255	SCV002739472	uncertain significance	Cardiovascular phenotype	2018-11-05	criteria provided, single submitter	clinical testing	The p.R89C variant (also known as c.265C>T), located in coding exon 3 of the SCN1B gene, results from a C to T substitution at nucleotide position 265. The arginine at codon 89 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV003483751	SCV004232391	likely pathogenic	Epileptic encephalopathy	2024-01-11	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989622	SCV004807983	likely pathogenic	Developmental and epileptic encephalopathy, 52	2024-03-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001766822	SCV005433303	likely pathogenic	not provided	2024-09-01	criteria provided, single submitter	clinical testing	SCN1B: PM2, PM3, PP1, PS3:Supporting