ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1393G>A (p.Val465Ile)

gnomAD frequency: 0.00002  dbSNP: rs139158852
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001765749 SCV001999384 uncertain significance not provided 2024-01-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882893 SCV002174394 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 465 of the CLCN1 protein (p.Val465Ile). This variant is present in population databases (rs139158852, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1309580). 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 CLCN1 protein function with a negative predictive value of 95%. 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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