ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.42C>G (p.Asn14Lys)

dbSNP: rs1262031967
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001058722 SCV001223313 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2022-11-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 853830). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asn14 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 23279342, 29998508; Invitae), which suggests that this may be a clinically significant amino acid residue. 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 GJB1 protein function. This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 9361298, 31323543). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 14 of the GJB1 protein (p.Asn14Lys).
Institute of Human Genetics, University of Goettingen RCV001310077 SCV001486206 likely pathogenic Charcot-Marie-Tooth disease X-linked dominant 1 2021-03-05 criteria provided, single submitter clinical testing This variant was found during routine testing. It is absent from control studies and is not described before. another AA change on that position is classified as pathogenic. In summary and using ACMG criteria PS1, PM2, PP2, PP3 this variant was classified as likely pathogeic.

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.