ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.1176G>T (p.Gly392=) (rs1051360)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000152898 SCV000202325 benign not specified 2018-01-02 criteria provided, single submitter clinical testing
Invitae RCV000233581 SCV000285584 benign Long QT syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000244258 SCV000318139 likely benign Cardiovascular phenotype 2016-01-22 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV000387297 SCV000377780 likely benign Timothy syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000295453 SCV000377781 likely benign Brugada syndrome 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718424 SCV000849287 likely benign History of neurodevelopmental disorder 2016-01-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Integrated Genetics/Laboratory Corporation of America RCV000152898 SCV001363277 benign not specified 2019-05-13 criteria provided, single submitter clinical testing Variant summary: CACNA1C c.1176G>T alters a 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 0.002 in 248890 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 196 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 benign. The variant, c.1176G>T, has been reported in the literature in individuals affected with long-QT syndrome (Ghouse_2015, Wemhoner_2015). These reports do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign (n=2), likely benign (n=2)). Based on the evidence outlined above, the variant was classified as benign.

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