ClinVar Miner

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

dbSNP: rs369773321
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) 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 2021-12-02 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 190 of the CLCN1 protein (p.Gly190Arg). This variant is present in population databases (rs369773321, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive myotonia congenita (Becker disease) (PMID: 23810313, 24037712, 24349310). ClinVar contains an entry for this variant (Variation ID: 289004). 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. This variant disrupts the p.Gly190 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19697366, 22921319, 23933576). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 Center for Human Genetics Tuebingen RCV000711236 SCV001248202 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000711236 SCV001822902 likely pathogenic not provided 2021-04-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22987687, 32670189, 23810313, 24037712, 24349310, 29606556)
PerkinElmer Genomics RCV000711236 SCV002022569 likely pathogenic not provided 2020-05-28 no assertion criteria provided 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.