Submissions for variant NM_001127222.2(CACNA1A):c.6650_6658del (p.His2217_His2219del)

dbSNP: rs776181081

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481504	SCV000571387	benign	not provided	2020-05-04	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-frame deletion in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000534340	SCV000656797	uncertain significance	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2017-09-01	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with CACNA1A-related disease. ClinVar contains an entry for this variant (Variation ID: 422029). While this variant is present in population databases (rs776181081), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant, c.6653_6661delACCACCATC, results in the deletion of 3 amino acid(s) of the CACNA1A protein (p.His2218_His2220del), but otherwise preserves the integrity of the reading frame.
Ambry Genetics	RCV002313252	SCV000847634	likely benign	Inborn genetic diseases	2017-09-07	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.
PreventionGenetics, part of Exact Sciences	RCV003985363	SCV004764826	likely benign	CACNA1A-related disorder	2019-11-04	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).