Submissions for variant NM_201596.3(CACNB2):c.1785C>T (p.His595=)

gnomAD frequency: 0.00879  dbSNP: rs61733967

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124110	SCV000167519	benign	not specified	2014-01-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206606	SCV000259569	benign	Brugada syndrome 4	2025-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000585972	SCV000700054	benign	not provided	2016-01-13	criteria provided, single submitter	clinical testing	Variant summary: The c.1623C>T variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 5/5 in silico tools via Alamut predict no significant effect on splicing. This variant is found in 317/121328 control chromosomes (5 homozygotes) at a frequency of 0.0026128, which is about 261 times of maximal expected frequency of a pathogenic allele (0.00001), suggesting this variant is benign. In addition, one clinical laboratory classified this variant as benign. The variant of interest has been found in one individual with co-occurrence of KCNQ1 c.674C>T/p.S225L (pathogenic) in our laboratory. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/other clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign.
Ambry Genetics	RCV000620127	SCV000735235	benign	Cardiovascular phenotype	2015-07-15	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000206606	SCV000743846	benign	Brugada syndrome 4	2016-08-24	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000206606	SCV002798036	likely benign	Brugada syndrome 4	2022-02-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000585972	SCV005320482	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000124110	SCV001920457	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975099	SCV004798712	benign	CACNB2-related disorder	2019-05-03	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).