Submissions for variant NM_000719.7(CACNA1C):c.5609C>T (p.Thr1870Met)

gnomAD frequency: 0.00102  dbSNP: rs201777030

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171802	SCV000050809	benign	not specified	2013-06-24	criteria provided, single submitter	research
Invitae	RCV001083389	SCV000252724	benign	Long QT syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587387	SCV000697553	benign	not provided	2016-10-26	criteria provided, single submitter	clinical testing	Variant summary: The c.5609C>T (p.Thr1870Met) in CACNA1C gene is a missense change that involves a highly conserved nucleotide and 3/4 in silico tools predict deleterious outcome. The variant of interest is located outside of any known functional domain, although the functional impact of this missense change is yet to be studied. The variant is present in the large control population dataset of ExAC at a frequency 0.003 (359/119184 chrs tested, including 1 homozygote), which exceeds the maximal expected frequency of a pathogenic allele (0.00001) in this gene. The variant has been reported in multiple affected individuals as well as in numerous unaffected controls. Lastly, it has been reported as Benign by several reputable databases/clinical laboratories. Taken together, the variant was classified as Benign.
Ambry Genetics	RCV000619639	SCV000735312	benign	Cardiovascular phenotype	2016-02-15	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.
GeneDx	RCV000587387	SCV001945224	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30403697, 27920829)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587387	SCV003799565	likely benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000587387	SCV001741696	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171802	SCV001956754	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000171802	SCV001978750	benign	not specified		no assertion criteria provided	clinical testing