ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.4623+13G>A

gnomAD frequency: 0.00241  dbSNP: rs111734850
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001420850 SCV001623260 benign not specified 2021-05-03 criteria provided, single submitter clinical testing Variant summary: CACNA1C c.4623+13G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00074 in 230660 control chromosomes, predominantly at a frequency of 0.0065 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 650 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Timothy Syndrome phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.4623+13G>A in individuals affected with Timothy Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV001711912 SCV001945195 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002056287 SCV002402789 benign Long QT syndrome 2024-01-28 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001711912 SCV005234715 benign not provided criteria provided, single submitter not provided

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