Submissions for variant NM_000719.7(CACNA1C):c.4317C>T (p.Asn1439=)

gnomAD frequency: 0.00058  dbSNP: rs183192651

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000427393	SCV000515771	benign	not specified	2015-06-10	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.
Invitae	RCV000462274	SCV000562883	likely benign	Long QT syndrome	2023-12-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621538	SCV000737477	likely benign	Cardiovascular phenotype	2016-02-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000427393	SCV000919077	benign	not specified	2017-09-18	criteria provided, single submitter	clinical testing	Variant summary: The CACNA1C c.4317C>T (p.Asn1439Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 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 42/276920 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.001666 (40/24008). This frequency is about 167 times the estimated maximal expected allele frequency of a pathogenic CACNA1C variant (0.00001), 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 benign/likely 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001810902	SCV002047747	likely benign	not provided	2020-10-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902490	SCV004727380	likely benign	CACNA1C-related disorder	2019-08-09	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).