ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6680G>A (p.Arg2227His)

dbSNP: rs1064793075
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796030 SCV000935521 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-01-04 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 2228 of the CACNA1A protein (p.Arg2228His). This variant is present in population databases (no rsID available, gnomAD 0.009%). This missense change has been observed in individuals with clinical features of CACNA1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 642549). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV001578054 SCV001805577 likely benign not provided 2020-07-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002537017 SCV003695493 likely benign Inborn genetic diseases 2022-08-03 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.
Revvity Omics, Revvity RCV001578054 SCV003830286 uncertain significance not provided 2021-04-07 criteria provided, single submitter clinical testing

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