ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.593T>C (p.Leu198Pro)

dbSNP: rs1347382107
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000711237 SCV000841569 likely pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001861960 SCV002235743 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-10-25 criteria provided, single submitter clinical testing 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. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu198 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15241802, 23113340; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 26096614). ClinVar contains an entry for this variant (Variation ID: 585692). This missense change has been observed in individuals with autosomal dominant myotonia congenita (PMID: 23483815, 26096614). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 198 of the CLCN1 protein (p.Leu198Pro).

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.