ClinVar Miner

Submissions for variant NM_004366.6(CLCN2):c.1543G>C (p.Val515Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004444242 SCV004928061 uncertain significance Inborn genetic diseases 2024-01-08 criteria provided, single submitter clinical testing The c.1543G>C (p.V515L) alteration is located in exon 15 (coding exon 15) of the CLCN2 gene. This alteration results from a G to C substitution at nucleotide position 1543, causing the valine (V) at amino acid position 515 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005038671 SCV005665060 uncertain significance Epilepsy, idiopathic generalized, susceptibility to, 11; Familial hyperaldosteronism type II; Leukoencephalopathy with mild cerebellar ataxia and white matter edema 2024-02-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005065090 SCV005717234 uncertain significance not provided 2024-02-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 515 of the CLCN2 protein (p.Val515Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CLCN2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CLCN2 protein function with a negative predictive value of 80%. 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.

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