ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1306G>A (p.Glu436Lys)

gnomAD frequency: 0.00004  dbSNP: rs759782636
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001051471 SCV001215626 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2022-03-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 437 of the CACNA1A protein (p.Glu437Lys). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 847841). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.
GeneDx RCV001759985 SCV001989841 uncertain significance not provided 2019-05-20 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002497405 SCV002778636 uncertain significance Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42 2022-02-10 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001759985 SCV004229447 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) This variant has been seen where an alternate explanation for disease was also identified, suggesting this variant may not cause disease. Computational tools predict that this variant is damaging.

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