ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1357G>A (p.Ala453Thr)

gnomAD frequency: 0.00451  dbSNP: rs41276886
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174037 SCV000225270 benign not specified 2014-10-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000059290 SCV000511112 likely benign not provided 2016-09-26 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
GeneDx RCV000174037 SCV000512439 benign not specified 2016-09-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000174037 SCV000538548 benign not specified 2016-10-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is present in ExAC at a MaxMAF of 2% in Finnish chromosomes. It is classified in ClinVar with 1 star as Benign by Emory and Likely Benign by UniProtKB/Swiss-Prot. It was reported in one patient with alternating hemiplagia of childhood who also had a de novo variant in ATP1A3, CACNA1A variant was also seen in her unaffected mother. It was seen in one family with Familial hemiplegic migraine (segregated in 1 relative) and was associated with the absence of sensorimotor symptoms in a migraine with aura. In the same paper, authors show via in vitro studies that this variant affected protein function. Was also seen in one proband with early-onset progressive ataxia and her affected sister. If this variant plays any role in disease, its frequnecy is too high to be a Mendelian variant.
Invitae RCV001083664 SCV000656710 benign Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-02-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000059290 SCV000841240 benign not provided 2017-09-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002313741 SCV000848039 benign Inborn genetic diseases 2016-09-13 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Mendelics RCV000990169 SCV001141014 benign Episodic ataxia type 2 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000059290 SCV002543889 benign not provided 2024-04-01 criteria provided, single submitter clinical testing CACNA1A: PP2, BS1, BS2
Fulgent Genetics, Fulgent Genetics RCV002504977 SCV002795182 likely benign Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42 2022-01-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003985265 SCV004720639 likely benign CACNA1A-related disorder 2020-07-23 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
UniProtKB/Swiss-Prot RCV000059290 SCV000090839 likely benign not provided no assertion criteria provided not provided Converted during submission to Likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000059290 SCV001744465 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000174037 SCV001975974 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000059290 SCV002034202 likely benign not provided no assertion criteria provided clinical testing

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