ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2026G>C (p.Glu676Gln)

gnomAD frequency: 0.00002  dbSNP: rs750187204
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484331 SCV000572988 uncertain significance not provided 2018-11-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLCN1 gene. The E676Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E676Q variant is observed in 5/78802 (0.01%) alleles from individuals of non-Finnish European background (Lek et al., 2016). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant..
Labcorp Genetics (formerly Invitae), Labcorp RCV001202235 SCV001373340 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 676 of the CLCN1 protein (p.Glu676Gln). This variant is present in population databases (rs750187204, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 423307). 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 not expected to disrupt CLCN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV000484331 SCV003830698 uncertain significance not provided 2021-12-06 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.