ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2233A>G (p.Asn745Asp)

gnomAD frequency: 0.00001  dbSNP: rs745586869
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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 RCV001973491 SCV002266609 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 745 of the CLCN1 protein (p.Asn745Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs745586869, ExAC 0.02%). This variant has not been reported in the literature in individuals with CLCN1-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 CLCN1 protein function. 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.
GeneDx RCV002307823 SCV002601182 uncertain significance not provided 2022-11-08 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

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