ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2172G>T (p.Glu724Asp)

gnomAD frequency: 0.00001  dbSNP: rs753308829
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 RCV002002953 SCV002271771 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-02-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 724 of the CLCN1 protein (p.Glu724Asp). This variant also falls at the last nucleotide of exon 17, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of autosomal recessive myotonia congenita (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1482531). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Fulgent Genetics, Fulgent Genetics RCV002002953 SCV005667252 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-04-17 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.