ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.1414G>A (p.Glu472Lys)

gnomAD frequency: 0.00001  dbSNP: rs770480382
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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 RCV002317459 SCV000850837 uncertain significance Cardiovascular phenotype 2017-02-28 criteria provided, single submitter clinical testing The p.E472K variant (also known as c.1414G>A), located in coding exon 10 of the CACNA1C gene, results from a G to A substitution at nucleotide position 1414. The glutamic acid at codon 472 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001862071 SCV002152371 uncertain significance Long QT syndrome 2023-03-26 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1C protein function. ClinVar contains an entry for this variant (Variation ID: 589746). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 472 of the CACNA1C protein (p.Glu472Lys).

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