ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.6650_6661del (p.His2217_His2220del) (rs770368215)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483925 SCV000570283 uncertain significance not specified 2017-06-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1A gene. The c.6650_6661del12 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 5,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.6650_6661del12 variant results in an in-frame deletion of 4 Histidine residues, denoted p.His2217_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 RCV000527151 SCV000656796 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2017-09-12 criteria provided, single submitter clinical testing This variant, c.6650_6661delACCACCACCATC, results in the deletion of 4 amino acid(s) of the CACNA1A protein (p.His2217_His2220del), but otherwise preserves the integrity of the reading frame. While this variant is present in population databases (rs770368215), 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 a CACNA1A-related disease. ClinVar contains an entry for this variant (Variation ID: 421166). 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, this variant has uncertain impact on CACNA1A function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996773 SCV001151689 likely benign not provided 2017-01-01 criteria provided, single submitter clinical testing

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