ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1655A>G (p.Gln552Arg) (rs80356696)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498537 SCV000589659 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing Reported as a heterozygous variant in a family with mild to moderate myotonia of bulbar muscles and miminal myotonia of arm and leg muscles (Lehmann-Horn et al., 1995); Published functional studies demonstrate a weak dominant negative effect and alteration of channel gating properties (Ryan et al., 2002); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18579381, 12210360, 18263754, 27324117, 12456816, 7581380, 8533761, 10619717, 11840191, 11933197, 24349310, 15786415, 9736777, 8845168, 12456818, 32670189)
Athena Diagnostics Inc RCV000498537 SCV000612769 pathogenic not provided 2017-05-11 criteria provided, single submitter clinical testing
Invitae RCV000685420 SCV000812899 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 552 of the CLCN1 protein (p.Gln552Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of autosomal dominant myotonia congenita (PMID: 7581380, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17538). This variant has been reported to affect CLCN1 protein function (PMID: 8845168, 12456816). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000498537 SCV001248211 pathogenic not provided 2018-07-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001253100 SCV001428631 likely pathogenic Congenital myotonia, autosomal dominant form 2017-06-23 criteria provided, single submitter clinical testing
OMIM RCV000019090 SCV000039378 pathogenic Myotonia levior 2002-12-01 no assertion criteria provided literature only
GeneReviews RCV000020103 SCV000040423 pathologic Myotonia congenita 2011-04-12 no assertion criteria provided curation Converted during submission to Pathogenic.

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