ClinVar Miner

Submissions for variant NM_004366.6(CLCN2):c.1412G>A (p.Arg471His)

gnomAD frequency: 0.00004  dbSNP: rs771507094
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002277555 SCV002567558 likely pathogenic not provided 2022-02-01 criteria provided, single submitter clinical testing Published functional studies demonstrate a decrease in CLCN2 current activation (Gaitan-Penas et al. 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 28905383, 28746943)
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003992233 SCV004809540 likely pathogenic Familial hyperaldosteronism type II 2024-04-04 criteria provided, single submitter clinical testing
GeneReviews RCV000201810 SCV000256588 not provided Leukoencephalopathy with mild cerebellar ataxia and white matter edema no assertion provided literature only
PreventionGenetics, part of Exact Sciences RCV004553102 SCV004796850 pathogenic CLCN2-related disorder 2024-01-31 no assertion criteria provided clinical testing The CLCN2 c.1412G>A variant is predicted to result in the amino acid substitution p.Arg471His. This variant has been reported in the homozygous state in one patient with gait-speech difficulty, dysarthria, nystagmus, ataxic gait, dysmetria and brain MRI findings consistent with CLCN2-related disease (Patient 1, Zeydan et al. 2017. PubMed ID: 28746943). This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD. In vitro functional characterization showed that this variant leads to significantly reduced current when compared to controls (Gaitán-Peñas. 2017. PubMed ID: 28905383). This variant is interpreted as pathogenic.

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