ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.6653_6661del (p.His2218_His2220del) (rs776181081)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481504 SCV000571387 uncertain significance not provided 2018-10-30 criteria provided, single submitter clinical testing The c.6653_6661delACCACCATC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.6653_6661delACCACCATC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.6653_6661delACCACCATC variant results in an in-frame deletion of 3 Histidine residues, denoted p.His2218_His2220del. However, it occurs at a position in a poly-Histidine repeat region and is not predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000534340 SCV000656797 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2017-07-17 criteria provided, single submitter clinical testing 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. 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 has not been reported in the literature in individuals with CACNA1A-related disease. ClinVar contains an entry for this variant (Variation ID: 422029). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. 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.
Ambry Genetics RCV000716791 SCV000847634 likely benign History of neurodevelopmental disorder 2017-09-07 criteria provided, single submitter clinical testing Other strong data supporting benign classification;Subpopulation frequency in support of benign classification

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