ClinVar Miner

Submissions for variant NM_004366.6(CLCN2):c.2642G>A (p.Arg881His)

gnomAD frequency: 0.00004  dbSNP: rs199616806
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001918490 SCV002177678 uncertain significance not provided 2024-03-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 881 of the CLCN2 protein (p.Arg881His). This variant is present in population databases (rs199616806, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CLCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1407525). 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 CLCN2 protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002484432 SCV002792437 uncertain significance Epilepsy, idiopathic generalized, susceptibility to, 11; Familial hyperaldosteronism type II; Leukoencephalopathy with mild cerebellar ataxia and white matter edema 2022-02-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV004611978 SCV005103612 uncertain significance Inborn genetic diseases 2024-06-17 criteria provided, single submitter clinical testing The c.2642G>A (p.R881H) alteration is located in exon 24 (coding exon 24) of the CLCN2 gene. This alteration results from a G to A substitution at nucleotide position 2642, causing the arginine (R) at amino acid position 881 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.