ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5477A>G (p.His1826Arg)

dbSNP: rs2055610097
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001066982 SCV001232008 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1827 of the CACNA1A protein (p.His1827Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 860639). 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 expected to disrupt CACNA1A protein function. 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.
GeneDx RCV001759838 SCV001987029 uncertain significance not provided 2023-07-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
3billion RCV002250722 SCV002521033 uncertain significance Developmental and epileptic encephalopathy, 42 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 0.73). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.

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