Submissions for variant NM_001127222.2(CACNA1A):c.3227C>T (p.Ala1076Val)

gnomAD frequency: 0.00024  dbSNP: rs199512932

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000996789	SCV000526293	likely benign	not provided	2020-08-04	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000996789	SCV000612526	likely benign	not provided	2019-09-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000559097	SCV000656747	likely benign	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2024-01-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002318451	SCV000850347	likely benign	Inborn genetic diseases	2019-01-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV000996789	SCV001151711	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	CACNA1A: PP2, BS1
Institute of Human Genetics, University of Leipzig Medical Center	RCV001253187	SCV001428779	uncertain significance	Developmental and epileptic encephalopathy, 42	2019-08-19	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224277	SCV003920645	uncertain significance	Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42	2021-03-30	criteria provided, single submitter	clinical testing	CACNA1A NM_001127221.1 exon 20 p.Ala1077Val (c.3230C>T): This variant has not been reported in the literature but is present in 37/124988 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs199512932). This variant is present in ClinVar (Variation ID:385136). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003985339	SCV004758075	likely benign	CACNA1A-related disorder	2023-06-19	no assertion criteria provided	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).