ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.5263G>A (p.Gly1755Arg) (rs1555737113)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547039 SCV000656772 likely pathogenic Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1755 of the CACNA1A protein (p.Gly1755Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with generalized epilepsy with typical absence seizures (PMID: 26795593). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000622365 SCV000740928 uncertain significance Inborn genetic diseases 2015-06-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected

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