ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2564G>A (p.Gly855Glu)

dbSNP: rs1554439879
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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 RCV000638243 SCV000759729 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-05-09 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported as heterozygous in combination with a second CLCN1 variant in an individual affected with myotonia (PMID: 26502825). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 855 of the CLCN1 protein (p.Gly855Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.
GeneDx RCV004723008 SCV005332519 uncertain significance not provided 2024-02-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29935101, 26502825, 33263785)

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