ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.680T>A (p.Ile227Asn)

dbSNP: rs1802446540
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV001509328 SCV001715968 uncertain significance not provided 2019-09-25 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001509328 SCV001880300 uncertain significance not provided 2020-10-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003771557 SCV004584606 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 227 of the CLCN1 protein (p.Ile227Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominan myotonia congenita (PMID: 28320154). ClinVar contains an entry for this variant (Variation ID: 1163875). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function with a positive predictive value of 80%. 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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