ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1831C>T (p.Arg611Cys)

gnomAD frequency: 0.00004  dbSNP: rs146469288
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000711225 SCV000841557 uncertain significance not provided 2018-08-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001358812 SCV001554664 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-02-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 611 of the CLCN1 protein (p.Arg611Cys). This variant is present in population databases (rs146469288, gnomAD 0.005%). 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: 585685). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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.
Neuberg Centre For Genomic Medicine, NCGM RCV003338743 SCV004048089 uncertain significance Congenital myotonia, autosomal recessive form criteria provided, single submitter clinical testing The missense variant c.1831C>T (p.Arg611Cys) has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Arg611Cys variant is reported with the allele frequency (0.001%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Arg at position 611 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The amino acid change p.Arg611Cys in CLCN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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