Submissions for variant NM_201596.3(CACNB2):c.1511C>T (p.Thr504Ile)

gnomAD frequency: 0.00181  dbSNP: rs143326262

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000170869	SCV000050763	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000170869	SCV000223424	likely benign	not provided	2022-10-17	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Invitae	RCV000231277	SCV000291906	likely benign	Brugada syndrome 4	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251462	SCV000319990	likely benign	Cardiovascular phenotype	2019-02-11	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000185500	SCV000538564	uncertain significance	not specified	2016-03-29	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: Only 1 proband in HGMD, ExAC: 0.2% (159/66588) European chromosomes
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000231277	SCV000743842	likely benign	Brugada syndrome 4	2017-06-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000185500	SCV000917105	benign	not specified	2017-12-18	criteria provided, single submitter	clinical testing	Variant summary: The CACNB2 c.1349C>T (p.Thr450Ile) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 449/289284 control chromosomes (1 homozygote), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.00279 (353/126520). This frequency is about 893 times the estimated maximal expected allele frequency of a pathogenic CACNB2 variant (0.0000031), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Though this variant has been reported in 2 individuals in a single family with BrS in an early study (Burashnikov 2010), later population studies indicated that the variant is not associated with BrS specific ECG patterns (Risgaard 2013, Ghouse 2017) and one study reports non-segregation of the variant with disease in a family (Allegue_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as benign.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852601	SCV000995304	likely benign	Ventricular tachycardia	2019-01-31	criteria provided, single submitter	clinical testing
Dept of Medical Biology, Uskudar University	RCV003318352	SCV004021967	benign	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: BS1, BS2
CeGaT Center for Human Genetics Tuebingen	RCV000170869	SCV004126524	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	CACNB2: BP4, BS1, BS2
CSER _CC_NCGL, University of Washington	RCV000148450	SCV000190149	uncertain significance	Brugada syndrome	2014-06-01	no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV000185500	SCV001925178	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000185500	SCV001955766	benign	not specified		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000170869	SCV003761505	not provided	not provided		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 11-08-2015 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.