ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1936A>T (p.Met646Leu)

dbSNP: rs1156766492
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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 RCV001939267 SCV002222888 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2021-11-02 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. 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. This variant disrupts the p.Met646 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18337730). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 646 of the CLCN1 protein (p.Met646Leu).

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