Submissions for variant NM_000719.7(CACNA1C):c.5360C>T (p.Thr1787Met)

gnomAD frequency: 0.00353  dbSNP: rs192749597

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124095	SCV000167504	benign	not specified	2013-10-07	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	RCV001080869	SCV000285595	benign	Long QT syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588907	SCV000697551	benign	not provided	2016-09-07	criteria provided, single submitter	clinical testing	Variant summary: The CACNA1C c.5360C>T (p.Thr1787Met) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 126/107256 control chromosomes (one homozygote), predominantly observed in the African subpopulation at a frequency of 0.0161245 (115/7132). This frequency is about 1612 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. This variant has been reported in three patients with arrhythmia in literature (Burashnikov_2010, Steffensen_2015, Wemhoner_2015), however without evidence for pathogenicity. One of the patients also carried a truncating variant in other gene, AKAP9 p.Thr3473AsnfsX3. Multiple clinical diagnostic laboratories have classified this variant as benign. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV000619661	SCV000735455	benign	Cardiovascular phenotype	2016-07-11	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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000355697	SCV000995371	benign	Brugada syndrome	2018-12-24	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588907	SCV005234728	benign	not provided		criteria provided, single submitter	not provided