ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.4140+4G>A (rs111442547)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617283 SCV000736118 likely benign Cardiovascular phenotype 2017-12-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000152903 SCV000202330 uncertain significance not provided 2014-03-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000354485 SCV000377854 uncertain significance Timothy syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000398544 SCV000377855 uncertain significance Brugada syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000631662 SCV000752745 uncertain significance Long QT syndrome 2018-07-09 criteria provided, single submitter clinical testing This sequence change falls in intron 33 of the CACNA1C gene. It does not directly change the encoded amino acid sequence of the CACNA1C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs111442547, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CACNA1C-related disease. ClinVar contains an entry for this variant (Variation ID: 166772). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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