ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.3547G>A (p.Val1183Ile) (rs369742607)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525516 SCV000656756 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2017-06-27 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1183 of the CACNA1A protein (p.Val1183Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs369742607, ExAC 0.03%) but has not been reported in the literature in individuals with a CACNA1A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000606877 SCV000728060 likely benign not specified 2018-03-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000710950 SCV000841265 likely benign not provided 2018-05-09 criteria provided, single submitter clinical testing

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