ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6730C>T (p.Arg2244Cys)

dbSNP: rs1021438528
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002318231 SCV000851507 uncertain significance Inborn genetic diseases 2017-01-26 criteria provided, single submitter clinical testing The p.R2245C variant (also known as c.6733C>T), located in coding exon 46 of the CACNA1A gene, results from a C to T substitution at nucleotide position 6733. The arginine at codon 2245 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001241664 SCV001414695 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2022-06-13 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: 590048). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2245 of the CACNA1A protein (p.Arg2245Cys).
GeneDx RCV001576611 SCV001803836 uncertain significance not provided 2021-04-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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