ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1910G>T (p.Gly637Val)

dbSNP: rs121908246
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000653334 SCV000775213 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2018-01-16 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 638 of the CACNA1A protein (p.Gly638Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant has not been reported in the literature in individuals with CACNA1A-related disease. 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. A different missense substitution at this codon (p.Gly638Asp) has been reported in individuals affected with episodic ataxia (PMID: 19232643, 28566750). 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.

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