ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6464G>A (p.Arg2155His)

dbSNP: rs572722130
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000761991 SCV000571570 uncertain significance not provided 2020-12-10 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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; This variant is associated with the following publications: (PMID: 32038460)
Ambry Genetics RCV002318579 SCV000851288 likely benign Inborn genetic diseases 2017-05-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen RCV000761991 SCV000892221 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
Invitae RCV002525898 SCV003240319 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2156 of the CACNA1A protein (p.Arg2156His). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 422167). 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 with a negative predictive value of 95%. 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.
Revvity Omics, Revvity RCV000761991 SCV003830303 uncertain significance not provided 2022-08-12 criteria provided, single submitter clinical testing

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