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

gnomAD frequency: 0.00451  dbSNP: rs41276886

Total submissions: 15

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 Inc	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: 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	2024-01-01	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