ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1649C>G (p.Thr550Arg)

dbSNP: rs762754992
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001312154 SCV001502615 pathogenic not provided 2022-03-01 criteria provided, single submitter clinical testing CLCN1: PM3:Strong, PM2, PM5, PP3, PP4
Labcorp Genetics (formerly Invitae), Labcorp RCV003770636 SCV004569617 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 550 of the CLCN1 protein (p.Thr550Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 21221019, 33263785). ClinVar contains an entry for this variant (Variation ID: 1013567). 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 95%. 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV003883175 SCV004697556 pathogenic Congenital myotonia, autosomal recessive form 2024-02-20 criteria provided, single submitter clinical testing

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