ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.848A>G (p.Asn283Ser)

gnomAD frequency: 0.00001  dbSNP: rs1212952550
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001996862 SCV002225427 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2021-12-29 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. 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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 283 of the CACNA1A protein (p.Asn283Ser).
Ambry Genetics RCV002407156 SCV002675364 uncertain significance Inborn genetic diseases 2018-07-16 criteria provided, single submitter clinical testing The p.N283S variant (also known as c.848A>G), located in coding exon 6 of the CACNA1A gene, results from an A to G substitution at nucleotide position 848. The asparagine at codon 283 is replaced by serine, an amino acid with highly similar properties. 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 alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002484767 SCV002781398 uncertain significance Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42 2021-09-27 criteria provided, single submitter clinical testing
GeneDx RCV002563499 SCV003195157 pathogenic not provided 2023-10-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34263451)

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