ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6776G>A (p.Arg2259Gln)

gnomAD frequency: 0.00001  dbSNP: rs201582095
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001204176 SCV001375371 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-03-08 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 CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 935553). This variant has not been reported in the literature in individuals affected with CACNA1A-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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2260 of the CACNA1A protein (p.Arg2260Gln).
Illumina Laboratory Services, Illumina RCV003985484 SCV001451649 uncertain significance CACNA1A-related disorder 2020-08-19 criteria provided, single submitter clinical testing The CACNA1A c.6779G>A (p.Arg2260Gln) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequence coverage in the genome dataset, so the variant is presumed to be rare. The p.Arg2260Gln variant is located in exon 46 of 47 in the cytoplasmic domain of the calcium voltage-gated channel subunit alpha1 A protein and in silico predictions of the consequence of this variant are mixed. Based on the limited evidence and application of the ACMG criteria, the p.Arg2260Gln variant is classified as a variant of uncertain significance for CACNA1A-related disorders.
GeneDx RCV002251557 SCV002522097 uncertain significance not provided 2021-11-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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