ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.563G>T (p.Gly188Val)

dbSNP: rs1554434857
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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 RCV000532409 SCV000636337 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-08-14 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 188 of the CLCN1 protein (p.Gly188Val). This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 31544778, 32593548). ClinVar contains an entry for this variant (Variation ID: 462846). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 24452722). This variant disrupts the p.Gly188 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been observed in individuals with CLCN1-related conditions (PMID: 23739125), which suggests that this may be a clinically significant amino acid residue. 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.

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