Submissions for variant NM_000719.7(CACNA1C):c.771C>T (p.Val257=)

gnomAD frequency: 0.00908  dbSNP: rs112315742

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079309	SCV000111179	benign	not specified	2013-07-23	criteria provided, single submitter	clinical testing
Invitae	RCV000227726	SCV000285605	benign	Long QT syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000248618	SCV000318481	benign	Cardiovascular phenotype	2016-07-14	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Ambry Genetics	RCV000717880	SCV000848740	benign	History of neurodevelopmental disorder	2016-07-14	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079309	SCV000919074	benign	not specified	2018-02-05	criteria provided, single submitter	clinical testing	Variant summary: CACNA1C c.771C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0029 in 271784 control chromosomes, predominantly within the African subpopulation at a frequency of 0.031, including 10 homozygotes in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 3000 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.771C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001636638	SCV001157278	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001636638	SCV001849514	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing