ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1943T>C (p.Leu648Pro)

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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 RCV003796914 SCV004585479 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-09-12 criteria provided, single submitter clinical testing 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. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with autosomal recessive myotonia (PMID: 33573884). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 648 of the CLCN1 protein (p.Leu648Pro).
GeneDx RCV004723482 SCV005333439 uncertain significance not provided 2023-12-13 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: 33573884)

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