Submissions for variant NM_001040151.2(SCN3B):c.328G>A (p.Val110Ile)

gnomAD frequency: 0.00029  dbSNP: rs147205617

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171068	SCV000050713	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000171068	SCV000223632	likely benign	not provided	2021-03-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27435932, 28747690, 27711072, 23257389, 30662450, 30821013, 30847666)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000185522	SCV000540270	uncertain significance	not specified	2016-08-12	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: Frequency high for disorder; Reported in 3 probands with no seg data; ClinVar: 2 VUS
Invitae	RCV001087315	SCV000562320	likely benign	Brugada syndrome 7	2024-01-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000185522	SCV000605062	uncertain significance	not specified	2017-03-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621217	SCV000736435	likely benign	Cardiovascular phenotype	2019-06-07	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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852659	SCV000995365	likely benign	Cardiomyopathy	2018-02-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000185522	SCV003844805	likely benign	not specified	2023-02-15	criteria provided, single submitter	clinical testing	Variant summary: SCN3B c.328G>A (p.Val110Ile) results in a conservative amino acid change located in the Immunoglobulin-like domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 251476 control chromosomes. The observed variant frequency is approximately 49 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN3B causing Arrhythmia phenotype (6.3e-06), strongly suggesting that the variant is benign. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=4, VUS n=2, pathogenic n=1). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003937532	SCV004758110	likely benign	SCN3B-related disorder	2022-04-26	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Forensic Genetics Laboratory, Harris County Institute of Forensic Sciences	RCV000234992	SCV000263111	pathogenic	Death in infancy	2015-03-27	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000171068	SCV001917171	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171068	SCV001956975	uncertain significance	not provided		no assertion criteria provided	clinical testing