Submissions for variant NM_033337.3(CAV3):c.-1G>A

gnomAD frequency: 0.00201  dbSNP: rs74377241

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039795	SCV000063484	likely benign	not specified	2012-12-18	criteria provided, single submitter	clinical testing	-1G>A in exon 1 of CAV3: This variant is not expected to have clinical significance because it has been identified in 0.6% (27/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed
Eurofins Ntd Llc (ga)	RCV000039795	SCV000114278	benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586122	SCV000699768	benign	not provided	2016-09-26	criteria provided, single submitter	clinical testing	Variant summary: The CAV3 c.-1G>A variant involves the alteration of a non-conserved nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 85/113904 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0086377 (79/9146). This frequency is about 346 times the estimated maximal expected allele frequency of a pathogenic CAV3 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000621195	SCV000736166	likely benign	Cardiovascular phenotype	2019-01-25	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.
Athena Diagnostics	RCV000586122	SCV000841369	benign	not provided	2017-08-25	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000586122	SCV000987388	likely benign	not provided		criteria provided, single submitter	clinical testing
GeneDx	RCV000586122	SCV001845097	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000039795	SCV001922483	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586122	SCV001973202	likely benign	not provided		no assertion criteria provided	clinical testing