ClinVar Miner

Submissions for variant NM_000722.4(CACNA2D1):c.1259G>A (p.Arg420Lys)

dbSNP: rs886039110
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000246425 SCV000320086 uncertain significance Cardiovascular phenotype 2015-09-04 criteria provided, single submitter clinical testing The p.R420K variant (also known as c.1259G>A), located in coding exon 14 of the CACNA2D1 gene, results from a G to A substitution at nucleotide position 1259. The arginine at codon 420 is replaced by lysine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5610 samples (11220 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002518716 SCV003000736 uncertain significance Brugada syndrome 2022-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 420 of the CACNA2D1 protein (p.Arg420Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA2D1-related conditions. ClinVar contains an entry for this variant (Variation ID: 264275). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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