ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.771C>T (p.Val257=) (rs112315742)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079309 SCV000111179 benign not specified 2013-07-23 criteria provided, single submitter clinical testing
Invitae RCV000227726 SCV000285605 benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000248618 SCV000318481 benign Cardiovascular phenotype 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
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
Integrated Genetics/Laboratory Corporation of America 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.

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