ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5057A>G (p.Gln1686Arg)

dbSNP: rs2055848608
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001307999 SCV001497431 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2020-01-15 criteria provided, single submitter clinical testing 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 (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. This variant has not been reported in the literature in individuals with CACNA1A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 1687 of the CACNA1A protein (p.Gln1687Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387990 SCV004099689 uncertain significance not specified 2023-09-01 criteria provided, single submitter clinical testing Variant summary: CACNA1A c.5060A>G (p.Gln1687Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249166 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5060A>G in individuals affected with Episodic Ataxia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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