ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1444G>C (p.Gly482Arg)

gnomAD frequency: 0.00003  dbSNP: rs746125212
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691722 SCV000819512 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2018-10-30 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. A different variant (c.1444G>A) giving rise to the same protein effect observed here (p.Gly482Arg) has been reported in individuals affected with autosomal recessive myotonia congenita (PMID:8533761, 22346025, 15311340), indicating that this residue may be critical for protein function. 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 C15"). This variant has been reported in the homozygous state in an individual affected with autosomal recessive myotonia congenita (Invitae). ClinVar contains an entry for this variant (Variation ID: 570776). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 482 of the CLCN1 protein (p.Gly482Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.

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