ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2255A>G (p.Lys752Arg)

dbSNP: rs2116386398
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001947334 SCV002133773 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2020-12-22 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has been observed in individual(s) with clinical features of myotonia congenita (PMID: 15241802). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 752 of the CLCN1 protein (p.Lys752Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine.

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.