ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.568G>A (p.Gly190Arg) (rs369773321)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000711236 SCV000343271 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing
Invitae RCV000530513 SCV000636298 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 190 of the CLCN1 protein (p.Gly190Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs369773321, ExAC 0.001%). This variant has been reported in combination with other CLCN1 variants in several individuals affected with autosomal recessive myotonia congenita (Becker disease) (PMID: 23810313, 24349310, 24037712). ClinVar contains an entry for this variant (Variation ID: 289004). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). A different missense substitution at this codon (p.Gly190Ser) has been determined to be pathogenic (PMID: 23933576, 19697366, 22921319). This suggests that the glycine residue is critical for CLCN1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000711236 SCV000841568 likely pathogenic not provided 2019-09-23 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000711236 SCV001248202 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.