ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2015G>C (p.Arg672Pro)

gnomAD frequency: 0.00001  dbSNP: rs777888721
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001884009 SCV002151219 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-03-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 672 of the CLCN1 protein (p.Arg672Pro). This variant is present in population databases (rs777888721, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected 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 RCV002553502 SCV003195262 uncertain significance not provided 2022-07-19 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
Ambry Genetics RCV002553501 SCV003544137 uncertain significance Inborn genetic diseases 2022-10-25 criteria provided, single submitter clinical testing The c.2015G>C (p.R672P) alteration is located in exon 17 (coding exon 17) of the CLCN1 gene. This alteration results from a G to C substitution at nucleotide position 2015, causing the arginine (R) at amino acid position 672 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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